Genetic coding in bacteria largely operates via the "one gene-one protein" paradigm. However, the peculiarities of the mRNA structure, the versatility of the genetic code, and the dynamic nature of translation sometimes allow organisms to deviate from the standard rules of protein encoding. Bacteria can use several unorthodox modes of translation to express more than one protein from a single mRNA cistron. One such alternative path is the use of additional translation initiation sites within the gene. Proteins whose translation is initiated at different start sites within the same reading frame will differ in their N termini but will have identical C-terminal segments. On the other hand, alternative initiation of translation in a register different from the frame dictated by the primary start codon will yield a protein whose sequence is entirely different from the one encoded in the main frame. The use of internal mRNA codons as translation start sites is controlled by the nucleotide sequence and the mRNA folding. The proteins of the alternative proteome generated via the "genes-within-genes" strategy may carry important functions. In this review, we summarize the currently known examples of bacterial genes encoding more than one protein due to the utilization of additional translation start sites and discuss the known or proposed functions of the alternative polypeptides in relation to the main protein product of the gene. We also discuss recent proteome- and genome-wide approaches that will allow the discovery of novel translation initiation sites in a systematic fashion.
Citation: Meydan S, Vázquez-Laslop N, Mankin A. 2018. Genes within Genes in Bacterial Genomes. Microbiol Spectrum 6(4):RWR-0020-2018. doi:10.1128/microbiolspec.RWR-0020-2018.
1. Atkins JF, Loughran G, Bhatt PR, Firth AE, Baranov PV. 2016. Ribosomal frameshifting and transcriptional slippage: from genetic steganography and cryptography to adventitious use. Nucleic Acids Res 44:7007–7078.
2. Baranov PV, Atkins JF, Yordanova MM. 2015. Augmented genetic decoding: global, local and temporal alterations of decoding processes and codon meaning. Nat Rev Genet 16:517–529. http://dx.doi.org/10.1038/nrg3963.
3. Caliskan N, Peske F, Rodnina MV. 2015. Changed in translation: mRNA recoding by -1 programmed ribosomal frameshifting. Trends Biochem Sci 40:265–274. http://dx.doi.org/10.1016/j.tibs.2015.03.006.
4. Dinman JD. 2012. Mechanisms and implications of programmed translational frameshifting. Wiley Interdiscip Rev RNA 3:661–673 http://dx.doi.org/10.1002/wrna.1126.
6. Doore SM, Baird CD, 2012 University of Arizona Virology Undergraduate Lab, Roznowski AP, Fane BA. 2014. The evolution of genes within genes and the control of DNA replication in microviruses. Mol Biol Evol 31:1421–1431. http://dx.doi.org/10.1093/molbev/msu089.
11. Vellanoweth RL, Rabinowitz JC. 1992. The influence of ribosome-binding-site elements on translational efficiency in Bacillus subtilis and Escherichia coli in vivo. Mol Microbiol 6:1105–1114. http://dx.doi.org/10.1111/j.1365-2958.1992.tb01548.x.
13. Accetto T, Avguštin G. 2011. Inability of Prevotella bryantii to form a functional Shine-Dalgarno interaction reflects unique evolution of ribosome binding sites in Bacteroidetes. PLoS One 6:e22914. http://dx.doi.org/10.1371/journal.pone.0022914.
14. Moll I, Grill S, Gualerzi CO, Bläsi U. 2002. Leaderless mRNAs in bacteria: surprises in ribosomal recruitment and translational control. Mol Microbiol 43:239–246. http://dx.doi.org/10.1046/j.1365-2958.2002.02739.x.
15. Salis HM. 2011. The ribosome binding site calculator. Methods Enzymol 498:19–42. http://dx.doi.org/10.1016/B978-0-12-385120-8.00002-4.
16. Valverde C, Haas D. 2008. Small RNAs controlled by two-component systems. Adv Exp Med Biol 631:54–79. http://dx.doi.org/10.1007/978-0-387-78885-2_5.
19. Sacerdot C, Dessen P, Hershey JW, Plumbridge JA, Grunberg-Manago M. 1984. Sequence of the initiation factor IF2 gene: unusual protein features and homologies with elongation factors. Proc Natl Acad Sci U S A 81:7787–7791. http://dx.doi.org/10.1073/pnas.81.24.7787.
21. Nyengaard NR, Mortensen KK, Lassen SF, Hershey JW, Sperling-Petersen HU. 1991. Tandem translation of E. coli initiation factor IF2β: purification and characterization in vitro of two active forms. Biochem Biophys Res Commun 181:1572–1579. http://dx.doi.org/10.1016/0006-291X(91)92118-4.
22. Sacerdot C, Vachon G, Laalami S, Morel-Deville F, Cenatiempo Y, Grunberg-Manago M. 1992. Both forms of translational initiation factor IF2 (α and β) are required for maximal growth of Escherichia coli: evidence for two translational initiation codons for IF2β. J Mol Biol 225:67–80. http://dx.doi.org/10.1016/0022-2836(92)91026-L.
23. Laursen BS, de A Steffensen SA, Hedegaard J, Moreno JM, Mortensen KK, Sperling-Petersen HU. 2002. Structural requirements of the mRNA for intracistronic translation initiation of the enterobacterial infB gene. Genes Cells 7:901–910. http://dx.doi.org/10.1046/j.1365-2443.2002.00571.x.
24. Shazand K, Tucker J, Chiang R, Stansmore K, Sperling-Petersen HU, Grunberg-Manago M, Rabinowitz JC, Leighton T. 1990. Isolation and molecular genetic characterization of the Bacillus subtilis gene ( infB) encoding protein synthesis initiation factor 2. J Bacteriol 172:2675–2687. http://dx.doi.org/10.1128/jb.172.5.2675-2687.1990.
25. Caserta E, Tomsic J, Spurio R, La Teana A, Pon CL, Gualerzi CO. 2006. Translation initiation factor IF2 interacts with the 30 S ribosomal subunit via two separate binding sites. J Mol Biol 362:787–799. http://dx.doi.org/10.1016/j.jmb.2006.07.043.
27. Madison KE, Abdelmeguid MR, Jones-Foster EN, Nakai H. 2012. A new role for translation initiation factor 2 in maintaining genome integrity. PLoS Genet 8:e1002648. http://dx.doi.org/10.1371/journal.pgen.1002648.
28. Madison KE, Jones-Foster EN, Vogt A, Kirtland Turner S, North SH, Nakai H. 2014. Stringent response processes suppress DNA damage sensitivity caused by deficiency in full-length translation initiation factor 2 or PriA helicase. Mol Microbiol 92:28–46. http://dx.doi.org/10.1111/mmi.12538.
29. North SH, Kirtland SE, Nakai H. 2007. Translation factor IF2 at the interface of transposition and replication by the PriA-PriC pathway. Mol Microbiol 66:1566–1578.
30. Li GW, Burkhardt D, Gross C, Weissman JS. 2014. Quantifying absolute protein synthesis rates reveals principles underlying allocation of cellular resources. Cell 157:624–635. http://dx.doi.org/10.1016/j.cell.2014.02.033.
31. Hénaut A, Lisacek F, Nitschké P, Moszer I, Danchin A. 1998. Global analysis of genomic texts: the distribution of AGCT tetranucleotides in the Escherichia coli and Bacillus subtilis genomes predicts translational frameshifting and ribosomal hopping in several genes. Electrophoresis 19:515–527. http://dx.doi.org/10.1002/elps.1150190411.
34. Subbarayan PR, Sarkar M. 2004. Escherichia coli rpoS gene has an internal secondary translation initiation region. Biochem Biophys Res Commun 313:294–299. http://dx.doi.org/10.1016/j.bbrc.2003.11.132.
35. Subbarayan PR, Sarkar M. 2004. A stop codon-dependent internal secondary translation initiation region in Escherichia coli rpoS. RNA 10:1359–1365. http://dx.doi.org/10.1261/rna.7500604.
36. Kato J, Suzuki H, Hirota Y. 1984. Overlapping of the coding regions for alpha and gamma components of penicillin-binding protein 1 b in Escherichia coli. Mol Gen Genet 196:449–457. http://dx.doi.org/10.1007/BF00436192.
37. Nakagawa J, Matsuhashi M. 1982. Molecular divergence of a major peptidoglycan synthetase with transglycosylase-transpeptidase activities in Escherichia coli—penicillin-binding protein 1Bs. Biochem Biophys Res Commun 105:1546–1553. http://dx.doi.org/10.1016/0006-291X(82)90964-0.
38. Henderson TA, Dombrosky PM, Young KD. 1994. Artifactual processing of penicillin-binding proteins 7 and 1b by the OmpT protease of Escherichia coli. J Bacteriol 176:256–259. http://dx.doi.org/10.1128/jb.176.1.256-259.1994.
39. Broome-Smith JK, Edelman A, Yousif S, Spratt BG. 1985. The nucleotide sequences of the ponA and ponB genes encoding penicillin-binding protein 1A and 1B of Escherichia coli K12. Eur J Biochem 147:437–446. http://dx.doi.org/10.1111/j.1432-1033.1985.tb08768.x.
40. Zijderveld CA, Aarsman ME, den Blaauwen T, Nanninga N. 1991. Penicillin-binding protein 1B of Escherichia coli exists in dimeric forms. J Bacteriol 173:5740–5746. http://dx.doi.org/10.1128/jb.173.18.5740-5746.1991.
41. Ünal CM, Steinert M. 2015. FKBPs in bacterial infections. Biochim Biophys Acta 1850:2096–2102. http://dx.doi.org/10.1016/j.bbagen.2014.12.018.
42. Mo YY, Seshu J, Wang D, Mallavia LP. 1998. Synthesis in Escherichia coli of two smaller enzymically active analogues of Coxiella burnetii macrophage infectivity potentiator (CbMip) protein utilizing a single open reading frame from the cbmip gene. Biochem J 335:67–77. http://dx.doi.org/10.1042/bj3350067.
44. Kittendorf JD, Sherman DH. 2009. The methymycin/pikromycin pathway: a model for metabolic diversity in natural product biosynthesis. Bioorg Med Chem 17:2137–2146. http://dx.doi.org/10.1016/j.bmc.2008.10.082.
45. Almutairi MM, Svetlov MS, Hansen DA, Khabibullina NF, Klepacki D, Kang HY, Sherman DH, Vázquez-Laslop N, Polikanov YS, Mankin AS. 2017. Co-produced natural ketolides methymycin and pikromycin inhibit bacterial growth by preventing synthesis of a limited number of proteins. Nucleic Acids Res 45:9573–9582. http://dx.doi.org/10.1093/nar/gkx673.
47. Hori T, Maezawa I, Nagahama N, Suzuki M. 1971. Isolation and structure of narbonolide, narbomycin, aglycone, from Streptomyces venezuelae and its biological transformation into picromycin via narbomycin. J Chem Soc D Chem Commun 0:304–305. http://dx.doi.org/10.1039/c29710000304.
48. Lambalot RH, Cane DE. 1992. Isolation and characterization of 10-deoxymethynolide produced by Streptomyces venezuelae. J Antibiot (Tokyo) 45:1981–1982. http://dx.doi.org/10.7164/antibiotics.45.1981.
49. Zabrocka E, Wegrzyn K, Konieczny I. 2014. Two replication initiators—one mechanism for replication origin opening? Plasmid 76:72–78. http://dx.doi.org/10.1016/j.plasmid.2014.10.003.
50. Shingler V, Thomas CM. 1984. Analysis of the trfA region of broad host-range plasmid RK2 by transposon mutagenesis and identification of polypeptide products. J Mol Biol 175:229–249. http://dx.doi.org/10.1016/0022-2836(84)90346-2.
51. Smith CA, Thomas CM. 1984. Nucleotide sequence of the trfA gene of broad host-range plasmid RK2. J Mol Biol 175:251–262. http://dx.doi.org/10.1016/0022-2836(84)90347-4.
52. Kittell BL, Helinski DR. 1991. Iteron inhibition of plasmid RK2 replication in vitro: evidence for intermolecular coupling of replication origins as a mechanism for RK2 replication control. Proc Natl Acad Sci U S A 88:1389–1393. http://dx.doi.org/10.1073/pnas.88.4.1389.
53. Durland RH, Helinski DR. 1987. The sequence encoding the 43-kilodalton trfA protein is required for efficient replication or maintenance of minimal RK2 replicons in Pseudomonas aeruginosa. Plasmid 18:164–169. http://dx.doi.org/10.1016/0147-619X(87)90044-8.
54. Konieczny I. 2003. Strategies for helicase recruitment and loading in bacteria. EMBO Rep 4:37–41. http://dx.doi.org/10.1038/sj.embor.embor703.
55. Zhong Z, Helinski D, Toukdarian A. 2003. A specific region in the N terminus of a replication initiation protein of plasmid RK2 is required for recruitment of Pseudomonas aeruginosa DnaB helicase to the plasmid origin. J Biol Chem 278:45305–45310. http://dx.doi.org/10.1074/jbc.M306058200.
56. Fang FC, Helinski DR. 1991. Broad-host-range properties of plasmid RK2: importance of overlapping genes encoding the plasmid replication initiation protein TrfA. J Bacteriol 173:5861–5868. http://dx.doi.org/10.1128/jb.173.18.5861-5868.1991.
57. Doyle SM, Genest O, Wickner S. 2013. Protein rescue from aggregates by powerful molecular chaperone machines. Nat Rev Mol Cell Biol 14:617–629. http://dx.doi.org/10.1038/nrm3660.
59. Squires CL, Pedersen S, Ross BM, Squires C. 1991. ClpB is the Escherichia coli heat shock protein F84.1. J Bacteriol 173:4254–4262. http://dx.doi.org/10.1128/jb.173.14.4254-4262.1991.
61. Impens F, Rolhion N, Radoshevich L, Bécavin C, Duval M, Mellin J, García Del Portillo F, Pucciarelli MG, Williams AH, Cossart P. 2017. N-terminomics identifies Prli42 as a membrane miniprotein conserved in Firmicutes and critical for stressosome activation in Listeria monocytogenes. Nat Microbiol 2:17005. http://dx.doi.org/10.1038/nmicrobiol.2017.5.
62. Chow IT, Baneyx F. 2005. Coordinated synthesis of the two ClpB isoforms improves the ability of Escherichia coli to survive thermal stress. FEBS Lett 579:4235–4241. http://dx.doi.org/10.1016/j.febslet.2005.06.054.
63. Eriksson MJ, Clarke AK. 1996. The heat shock protein ClpB mediates the development of thermotolerance in the cyanobacterium Synechococcus sp. strain PCC 7942. J Bacteriol 178:4839–4846. http://dx.doi.org/10.1128/jb.178.16.4839-4846.1996.
64. Nagy M, Guenther I, Akoyev V, Barnett ME, Zavodszky MI, Kedzierska-Mieszkowska S, Zolkiewski M. 2010. Synergistic cooperation between two ClpB isoforms in aggregate reactivation. J Mol Biol 396:697–707. http://dx.doi.org/10.1016/j.jmb.2009.11.059.
65. Clarke AK, Eriksson MJ. 2000. The truncated form of the bacterial heat shock protein ClpB/HSP100 contributes to development of thermotolerance in the cyanobacterium Synechococcus sp. strain PCC 7942. J Bacteriol 182:7092–7096. http://dx.doi.org/10.1128/JB.182.24.7092-7096.2000.
67. Seol JH, Yoo SJ, Kang MS, Ha DB, Chung CH. 1995. The 65-kDa protein derived from the internal translational start site of the clpA gene blocks autodegradation of ClpA by the ATP-dependent protease Ti in Escherichia coli. FEBS Lett 377:41–43. http://dx.doi.org/10.1016/0014-5793(95)01306-7.
68. Loh E, Righetti F, Eichner H, Twittenhoff C, Narberhaus F. 2018. RNA thermometers in bacterial pathogens. Microbiol Spectr 6:RWR-0012-2017. http://dx.doi.org/10.1128/microbiolspec.RWR-0012-2017.
70. Hwang J, Manuvakhova M, Tai PC. 1997. Characterization of in-frame proteins encoded by cvaA, an essential gene in the colicin V secretion system: CvaA* stabilizes CvaA to enhance secretion. J Bacteriol 179:689–696. http://dx.doi.org/10.1128/jb.179.3.689-696.1997.
73. Pieper U, Groll DH, Wünsch S, Gast FU, Speck C, Mücke N, Pingoud A. 2002. The GTP-dependent restriction enzyme McrBC from Escherichia coli forms high-molecular mass complexes with DNA and produces a cleavage pattern with a characteristic 10-base pair repeat. Biochemistry 41:5245–5254. http://dx.doi.org/10.1021/bi015687u.
74. Ross TK, Achberger EC, Braymer HD. 1989. Nucleotide sequence of the McrB region of Escherichia coli K-12 and evidence for two independent translational initiation sites at the mcrB locus. J Bacteriol 171:1974–1981. http://dx.doi.org/10.1128/jb.171.4.1974-1981.1989.
76. Panne D, Raleigh EA, Bickle TA. 1998. McrBs, a modulator peptide for McrBC activity. EMBO J 17:5477–5483. http://dx.doi.org/10.1093/emboj/17.18.5477.
78. Long BM, Badger MR, Whitney SM, Price GD. 2007. Analysis of carboxysomes from Synechococcus PCC7942 reveals multiple Rubisco complexes with carboxysomal proteins CcmM and CcaA. J Biol Chem 282:29323–29335. http://dx.doi.org/10.1074/jbc.M703896200.
79. Price GD, Sültemeyer D, Klughammer B, Ludwig M, Badger MR. 1998. The functioning of the CO 2 concentrating mechanism in several cyanobacterial strains: a review of general physiological characteristics, genes, proteins, and recent advances. Can J Bot 76:973–1002. http://dx.doi.org/10.1139/b98-081.
85. Song M, Sukovich DJ, Ciccarelli L, Mayr J, Fernandez-Rodriguez J, Mirsky EA, Tucker AC, Gordon DB, Marlovits TC, Voigt CA. 2017. Control of type III protein secretion using a minimal genetic system. Nat Commun 8:14737. http://dx.doi.org/10.1038/ncomms14737.
89. Wolfe AJ, Stewart RC. 1993. The short form of the CheA protein restores kinase activity and chemotactic ability to kinase-deficient mutants. Proc Natl Acad Sci U S A 90:1518–1522. http://dx.doi.org/10.1073/pnas.90.4.1518.
94. Lo CC, Bonner CA, Xie G, D'Souza M, Jensen RA. 2009. Cohesion group approach for evolutionary analysis of aspartokinase, an enzyme that feeds a branched network of many biochemical pathways. Microbiol Mol Biol Rev 73:594–651. http://dx.doi.org/10.1128/MMBR.00024-09.
99. Kallio P, Liu Z, Mäntsälä P, Niemi J, Metsä-Ketelä M. 2008. A nested gene in Streptomyces bacteria encodes a protein involved in quaternary complex formation. J Mol Biol 375:1212–1221. http://dx.doi.org/10.1016/j.jmb.2007.11.044.
100. Thomas CM, Smith CA. 1986. The trfB region of broad host range plasmid RK2: the nucleotide sequence reveals incC and key regulatory gene trfB/korA/korD as overlapping genes. Nucleic Acids Res 14:4453–4469. http://dx.doi.org/10.1093/nar/14.11.4453.
101. Batt SM, Bingle LE, Dafforn TR, Thomas CM. 2009. Bacterial genome partitioning: N-terminal domain of IncC protein encoded by broad-host-range plasmid RK2 modulates oligomerisation and DNA binding. J Mol Biol 385:1361–1374. http://dx.doi.org/10.1016/j.jmb.2008.12.016.
107. Malakooti J, Ely B, Matsumura P. 1994. Molecular characterization, nucleotide sequence, and expression of the fliO, fliP, fliQ, and fliR genes of Escherichia coli. J Bacteriol 176:189–197. http://dx.doi.org/10.1128/jb.176.1.189-197.1994.
110. Ebisu S, Tsuboi A, Takagi H, Naruse Y, Yamagata H, Tsukagoshi N, Udaka S. 1990. Conserved structures of cell wall protein genes among protein-producing Bacillus brevis strains. J Bacteriol 172:1312–1320. http://dx.doi.org/10.1128/jb.172.3.1312-1320.1990.
112. Ozin AJ, Costa T, Henriques AO, Moran CP Jr. 2001. Alternative translation initiation produces a short form of a spore coat protein in Bacillus subtilis. J Bacteriol 183:2032–2040. http://dx.doi.org/10.1128/JB.183.6.2032-2040.2001.
116. Blight MA, Menichi B, Holland IB. 1995. Evidence for post-transcriptional regulation of the synthesis of the Escherichia coli HlyB haemolysin translocator and production of polyclonal anti-HlyB antibody. Mol Gen Genet 247:73–85. http://dx.doi.org/10.1007/BF00425823.
117. Flores-Díaz M, Monturiol-Gross L, Naylor C, Alape-Girón A, Flieger A. 2016. Bacterial sphingomyelinases and phospholipases as virulence factors. Microbiol Mol Biol Rev 80:597–628. http://dx.doi.org/10.1128/MMBR.00082-15.
119. Shen BF, Tai PC, Pritchard AE, Vasil ML. 1987. Nucleotide sequences and expression in Escherichia coli of the in-phase overlapping Pseudomonas aeruginosa plcR genes. J Bacteriol 169:4602–4607. http://dx.doi.org/10.1128/jb.169.10.4602-4607.1987.
120. Buskirk AR, Green R. 2017. Ribosome pausing, arrest and rescue in bacteria and eukaryotes. Philos Trans R Soc Lond B Biol Sci 372:20160183. http://dx.doi.org/10.1098/rstb.2016.0183.
123. Hamoen LW, Eshuis H, Jongbloed J, Venema G, van Sinderen D. 1995. A small gene, designated comS, located within the coding region of the fourth amino acid-activation domain of srfA, is required for competence development in Bacillus subtilis. Mol Microbiol 15:55–63. http://dx.doi.org/10.1111/j.1365-2958.1995.tb02220.x.
125. Ogasawara N, Yoshikawa H. 1992. Genes and their organization in the replication origin region of the bacterial chromosome. Mol Microbiol 6:629–634. http://dx.doi.org/10.1111/j.1365-2958.1992.tb01510.x.
126. Feltens R, Gossringer M, Willkomm DK, Urlaub H, Hartmann RK. 2003. An unusual mechanism of bacterial gene expression revealed for the RNase P protein of Thermus strains. Proc Natl Acad Sci U S A 100:5724–5729. http://dx.doi.org/10.1073/pnas.0931462100.
127. Osterman IA, Evfratov SA, Sergiev PV, Dontsova OA. 2013. Comparison of mRNA features affecting translation initiation and reinitiation. Nucleic Acids Res 41:474–486. http://dx.doi.org/10.1093/nar/gks989.
128. Yuan P, D'Lima NG, Slavoff SA. 2018. Comparative membrane proteomics reveals a nonannotated E. coli heat shock protein. Biochemistry 57:56–60. http://dx.doi.org/10.1021/acs.biochem.7b00864.
129. Chang JT, Green CB, Wolf RE Jr. 1995. Inhibition of translation initiation on Escherichia coli gnd mRNA by formation of a long-range secondary structure involving the ribosome binding site and the internal complementary sequence. J Bacteriol 177:6560–6567. http://dx.doi.org/10.1128/jb.177.22.6560-6567.1995.
131. Bienvenut WV, Giglione C, Meinnel T. 2015. Proteome-wide analysis of the amino terminal status of Escherichia coli proteins at the steady-state and upon deformylation inhibition. Proteomics 15:2503–2518. http://dx.doi.org/10.1002/pmic.201500027.
132. Ingolia NT, Ghaemmaghami S, Newman JR, Weissman JS. 2009. Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling. Science 324:218–223. http://dx.doi.org/10.1126/science.1168978.
133. Schrader JM, Zhou B, Li GW, Lasker K, Childers WS, Williams B, Long T, Crosson S, McAdams HH, Weissman JS, Shapiro L. 2014. The coding and noncoding architecture of the Caulobacter crescentus genome. PLoS Genet 10:e1004463. http://dx.doi.org/10.1371/journal.pgen.1004463.
134. Fritsch C, Herrmann A, Nothnagel M, Szafranski K, Huse K, Schumann F, Schreiber S, Platzer M, Krawczak M, Hampe J, Brosch M. 2012. Genome-wide search for novel human uORFs and N-terminal protein extensions using ribosomal footprinting. Genome Res 22:2208–2218. http://dx.doi.org/10.1101/gr.139568.112.
136. Lee S, Liu B, Lee S, Huang SX, Shen B, Qian SB. 2012. Global mapping of translation initiation sites in mammalian cells at single-nucleotide resolution. Proc Natl Acad Sci U S A 109:E2424–E2432. http://dx.doi.org/10.1073/pnas.1207846109.
137. Nakahigashi K, Takai Y, Kimura M, Abe N, Nakayashiki T, Shiwa Y, Yoshikawa H, Wanner BL, Ishihama Y, Mori H. 2016. Comprehensive identification of translation start sites by tetracycline-inhibited ribosome profiling. DNA Res 23:193–201. http://dx.doi.org/10.1093/dnares/dsw008.
138. Davidovich C, Bashan A, Auerbach-Nevo T, Yaggie RD, Gontarek RR, Yonath A. 2007. Induced-fit tightens pleuromutilins binding to ribosomes and remote interactions enable their selectivity. Proc Natl Acad Sci U S A 104:4291–4296. http://dx.doi.org/10.1073/pnas.0700041104.
139. Yan K, Madden L, Choudhry AE, Voigt CS, Copeland RA, Gontarek RR. 2006. Biochemical characterization of the interactions of the novel pleuromutilin derivative retapamulin with bacterial ribosomes. Antimicrob Agents Chemother 50:3875–3881. http://dx.doi.org/10.1128/AAC.00184-06.
140. Florin T, Maracci C, Graf M, Karki P, Klepacki D, Berninghausen O, Beckmann R, Vázquez-Laslop N, Wilson DN, Rodnina MV, Mankin AS. 2017. An antimicrobial peptide that inhibits translation by trapping release factors on the ribosome. Nat Struct Mol Biol 24:752–757. http://dx.doi.org/10.1038/nsmb.3439.
Different strategies for encoding more than one protein in one gene. (a) The conventional one gene-one protein scenario. (b) Programmed ribosomal frameshifting results in translation of two proteins whose N-terminal sequences are the same but differ in their C-terminal segments. The alternative protein could be shorter or longer than the primary one depending on the position of the OOF stop codon. (c) Presence of an internal in-frame start codon within the ORF results in production of a truncated protein devoid of the N-terminal segment of the full-size translation product. If the internal start codon is OOF relative to the main ORF, the sequence of the alternative polypeptide is completely different from that of the protein encoded in the main ORF.
Internal initiation alters protein localization. Full-size Mip-23.5 protein carries a signal sequence (SS) at its N terminus, which predisposes it to be secreted. The products of internal initiation, Mip-15.5 and Mip-15.0, lack the signal sequence and, as a result, remain in the cytoplasm.
Alternative translation initiation accounts for production of two antibiotics by the same biochemical pathway. Production of the full-size PikAIV polyketide synthase module supports synthesis of the 14-atom macrolactone ring of pikromycin. The N-terminally truncated PikAIV variant leads to the synthesis of the smaller (12-atom) macrolactone ring of methymycin.
Alternative protein restores stoichiometry of the functional restriction enzyme. Full-size McrBL binds DNA and associates with the nucleolytic McrC to cleave DNA. McrBS lacks the N-terminal DNA-binding domain (dark blue) but is able to titrate out the excess McrC to maintain optimal activity of the restriction enzyme complex. The general scheme of the figure was adapted from reference 72 .
The isoforms of CcmM help to differentially organize RubisCO in β-carboxysome. The N-terminal segment of the full-size CcmM-58 (dark blue) anchors it to the inner shell of the β-carboxysome, while its C-terminal segment (light blue) arranges the first layer of RubisCO. The N-terminally truncated Ccm-35 organizes RubisCO into a lattice in the lumen of the β-carboxysome.
The alternative LysC isoform expands the amino acid-mediated regulation of the enzyme. The full-size (α) and N-terminally truncated (β) isoforms of LysC associate into a functional α2β2 tetramer, in which the binding sites for the regulatory amino acids lysine (orange) and threonine (red) are formed at the interface of the α-β subunits. Shown is the structure of Corynebacterium glutamicum LysC (PDB ID: 3AAW) ( 95 ).
Elimination of the stop codon creates a fused gene with two translation starts. Two genes, tilS and hprT, which encode functionally distinct proteins and associate to form a functional complex, are organized in an operon in B. subtilis. Due to the elimination of the tilS stop codon in L. monocytogenes, the two ORFs are fused into a single gene and can be expressed from the primary and the internal TIS.
The use of different promoters can regulate the utilization of alternative start sites within a gene. Two promoters (P1 and P2) precede the petH gene in Synechocystis 6803. The transcript initiated at P2 has a short 5′ UTR; the accessible pTIS favors translation of the full-size FNRL. Folding of the long 5′ UTR of the transcripts initiated at the P1 promoter occludes the pTIS, thereby shifting the relative expression of the FNR isoforms in favor of the shorter FNRS. While photosynthetic growth favors synthesis of FNRL, heterotrophic conditions stimulate production of the FNRS isoform.
Elimination of a start codon leads to gene occlusion. In E. coli, the neighboring genes of ribosomal protein L34 (rpmH) and RNase P protein (rnpA) are independently translated. In T. thermophilus, the mutation of the rnpA translation initiation codon and appearance of an additional start site upstream of rpmH lead to occlusion of rpmH within the rnpA gene, but in an alternative reading frame. Start sites of both genes utilize the same SD sequence (blue), whose optimal spacing with the rpmH start codon shifts the balance of translation in favor of the ribosomal protein.
Retapamulin-assisted ribosome profiling illuminates sites of internal translation initiation. (a) (Left) Ribosome profiling in untreated cells shows the distribution of translating ribosomes along the mRNAs ( 30 ). (Right) Brief pretreatment of cells with the translation initiation inhibitor retapamulin arrests the ribosomes at the translation start site of the ORFs. (b) Examples of primary and internal TISs revealed by retapamulin-assisted ribosome profiling in E. coli genes known to contain functional internal start codons. Note that the presence of the iTISs is difficult to detect when ribosome profiling is performed in untreated cells.


Tag Archives for " Internal Revenue Service "
Every now and then I get asked to provide a list of resources to help small business owners get started and growing. Here are some of my favorite recommendations.
SCORE – Service Corps of Retired Executives Find a SCORE chapter – Retired business owners volunteer and share wisdom.
StartUpNation – Resources to help you start your business and growing community of folks interested in starting.


text:
<?php

namespace Lug\Component\Grid\Batch\Type;

use Symfony\Component\OptionsResolver\OptionsResolver;

/**
 * @author GeLo <geloen.eric@gmail.com>
 */
abstract class AbstractType implements TypeInterface
{
    /**
     * {@inheritdoc}
     */
    public function configureOptions(OptionsResolver $resolver)
    {
    }

    /**
     * {@inheritdoc}
     */
    public function getParent()
    {
        return 'batch';
    }
}

redpajama_set_name: RedPajamaGithub


We are continuously putting out new trial data every year with the help of our largest suppliers. Click the links below to see varietal and agronomic trial done by ourselves and other dealers in SK and MB.
We hold an open house beginning of September to review our local plots and strip trials. As a thank you to our growers we offer a complimentary Sweet Corn U-Pick. This GMO, Round-up Ready, Corn Borer resistant sweet corn is some of the best tasting garden corn you will ever taste!