Figure 7–65 An experiment demonstrating the importance of the 3ʹ UTR in localizing mRNAs to specific regions of the cytoplasm. for this experiment, two different fluorescently labeled rnAs were prepared by transcribing DnA in vitro in the presence of fluorescently labeled derivatives of Utp. One rnA (labeled with a red fluorochrome) contains the coding region for the Drosophila hairy protein and includes the adjacent 3ʹ Utr (see figure 6–21). the other rnA (labeled green) contains the hairy coding region with the 3ʹ Utr deleted. the two rnAs were mixed and injected into a Drosophila embryo at a stage of development when multiple nuclei reside in a common cytoplasm (see figure 7–26). when the fluorescent rnAs were visualized 10 minutes later, the full-length hairy rnA (red) was localized to the apical side of nuclei (blue) but the transcript missing the 3ʹ Utr (green) failed to localize. hairy is one of many transcriptional regulators that specify positional information in the developing Drosophila embryo (discussed in Chapter 21), and the localization of its mrnA (shown in this experiment to depend on its 3ʹ Utr) is critical for proper fly development. (Courtesy of Simon Bullock and David ish-horowicz.) extends from the stop codon that terminates protein synthesis to the start of the poly-A tail (Figure 7–65). The mRNA localization is usually coupled with translational controls to ensure that the mRNA remains quiescent until it has been moved into place.
The Drosophila egg exhibits an especially striking example of mRNA localization. The mRNA encoding the Bicoid transcription regulator is localized by attachment to the cytoskeleton at the anterior tip of the developing egg. When fertilization triggers the translation of this mRNA, it generates a gradient of the Bicoid protein that plays a crucial part in directing the development of the anterior part of the embryo (see Figure 7–26). Many mRNAs in somatic cells are also localized in a similar way. The mRNA that encodes actin, for example, is localized to the actin-filament-rich cell cortex in mammalian fibroblasts by means of a 3ʹ UTR signal.
We saw in Chapter 6 that mRNA molecules exit from the nucleus bearing numerous markings in the form of RNA modifications (the 5ʹ cap and the 3ʹ poly-A tail) and bound proteins (exon-junction complexes, for example) that signify the successful completion of the different pre-mRNA processing steps. As just described, the 3ʹ UTR of an mRNA can be thought of as a “zip code” that directs mRNAs to different places in the cell. Below, we will also see that mRNAs carry information specifying their average lifetime in the cytosol and the efficiency with which they are translated into protein. In a broad sense, the untranslated regions of eukaryotic mRNAs resemble the transcriptional control regions of genes: their nucleotide sequences contain information specifying the way the RNA is to be used, and proteins interpret this information by binding specifically to these sequences. Thus, over and above the specification of the amino acid sequences of proteins, mRNA molecules are rich with information.
the 5ʹ and 3ʹ Untranslated regions of mrnAs Control their translation
Once an mRNA has been synthesized, one of the most common ways of regulating the levels of its protein product is to control the step that initiates translation. Even though the details of translation initiation differ between eukaryotes and bacteria (as we saw in Chapter 6), they each use some of the same basic regulatory strategies.
In bacterial mRNAs, a conserved stretch of nucleotides, the Shine–Dalgarno sequence, is always found a few nucleotides upstream of the initiating AUG codon. In bacteria, translational control mechanisms are carried out by proteins or by RNA molecules, and they generally involve either exposing or blocking the Shine– Dalgarno sequence (Figure 7–66).