In terms of biological function, lncRNA should be considered a catch-all phrase encompassing a great diversity of functions. Nevertheless, there are two unifying features of lncRNAs that can account for their many roles in the cell. The first is that lncRNAs can function as scaffold RNA molecules, holding together groups of proteins to coordinate their functions (Figure 7–79A). We have already seen an example in telomerase, where the RNA molecule holds together and organizes protein components. These RNA-based scaffolds are analogous to protein scaffolds we discussed in Chapter 3 (see Figure 3–78) and Chapter 6 (see Figure 6–47). RNA molecules are well suited to act as scaffolds: small bits of RNA sequence, often those portions that form stem-loop structures, can serve as binding sites for proteins, and these can be strung together with random sequences of RNA in between. This property may be one reason that lncRNAs show relatively little primary-sequence conservation across species.
The second key feature of lncRNAs is their ability to serve as guide sequences, binding to specific RNA or DNA target molecules through base-pairing. By doing so, they bring proteins that are bound to them into close proximity with the DNA
Figure 7–79 Roles of long noncoding RNA (lncRNA). (A) lncrnAs can serve as scaffolds, bringing together proteins that function in the same process. As described in Chapter 6, rnAs can fold into specific three-dimensional structures that are often recognized by proteins. (B) in addition to serving as scaffolds, lncrnAs can, through formation of complementary base pairs, localize proteins to specific sequences on rnA or DnA molecules. (C) in some cases, lncrnAs act only in cis, for example, when the rnA is held in place by rnA polymerase (top). Other lncrnAs, however, diffuse from their sites of synthesis and therefore act in trans.
(A) IncRNA IncRNA IncRNA RNA DNA RNA polymerase controls transcription of genes on same chromosome controls transcription of genes on other chromosomes, chromosome A chromosome A chromosome B ACTS IN CISACTS IN TRANS and RNA sequences (Figure 7–79B). This behavior is similar to that of snoRNAs (see Figure 6–41), crRNAs (see Figure 7–78), and miRNAs (see Figure 7–75), all of which act in this way to guide protein enzymes to specific nucleic acid sequences.
In some cases, lncRNAs work simply by base-pairing, without bringing in enzymes or other proteins. For example, a number of lncRNA genes are embedded in protein-coding genes, but they are transcribed in the “wrong direction.” These antisense RNAs can form complementary base pairs with the mRNA (transcribed in the “correct” direction) and block its translation into protein (see Figure 7–66D). Other antisense lncRNAs base-pair with pre-mRNAs as they are synthesized and change the pattern of RNA splicing by masking splice-site sequences. Still others act as “sponges,” base-pairing with miRNAs and thereby reducing their effects.
Finally, we note that some lncRNAs can act only in cis; that is, they affect only the chromosome from which they are transcribed. This readily occurs when the transcribed RNA has not yet been released from RNA polymerases (Figure 7–79C). Many lncRNAs, however, diffuse from their site of synthesis and act in trans. Although the best understood lncRNAs work in the nucleus, many are found in the cytosol. The functions—if any—of the great majority of these cytosolic lncRNAs remain undiscovered.