Xist is one example of the rapidly growing class of functional RNAs (see Chapter 8). Functional RNAs do not encode proteins: rather, they perform a variety of tasks that exploit the complementarity of RNA and RNA and of RNA and DNA. The functional RNAs discussed here contain specific sequences that direct proteins or protein complexes to places in the cell where their services are needed. For example, Xist acts to direct proteins involved in heterochromatin formation to one of the two X chromosomes.

Two types of small functional RNAs were introduced in Chapter 8: siRNAs and miRNAs. In this section we explore how miRNAs assist in the regulation of eukaryotic gene expression. The function of siRNAs will be considered further in Chapter 15.

Recall from Chapter 8 that miRNAs are synthesized by RNA pol II as longer RNAs that are processed into the smaller (~22 nt) biologically active miRNAs (see Figure 8-20). Organisms contain hundreds of miRNAs that regulate thousands of genes. Of these, about 1/3 are organized into clusters that are transcribed into a single transcript, which is later processed to form several miRNAs. In contrast, about 1/4 of all miRNAs are processed from transcripts derived from spliced introns. The final steps in the processing of miRNAs occurs in the cytoplasm.

In Chapter 8 we saw how the active single-stranded miRNAs bind to the RNA-inducing silencing complex (RISC) and hybridize to mRNAs that are complementary to the miRNAs. Specifically, the binding region of the miRNA consists of nucleotides 2 through 8 of the ~22-nt miRNA, called the seed region. The nucleotides of the seed region bind to the 3′UTR of an mRNA that is being translated by ribosomes (Figure 12-31). While the miRNA–RISC complex is known to inhibit translation, the precise mechanism is still under investigation. Models for how translation may be repressed include interference with translation initiation or elongation or the removal of the poly(A) tail, which would hasten mRNA degradation (Figure 12-31).

Although miRNAs were discovered almost 20 years ago, scientists are only beginning to decipher the extent and complexity of miRNA control of eukaryotic gene expression. Consider that in mammals, sequences complementary to the seed regions of miRNAs are found in the 3′ UTR of several hundred genes. Furthermore, the 3′UTRs of some genes contain sequences complementary to several miRNAs, while many miRNAs contain sequences complementary to the 3′ UTRs of several genes. Thus, one gene can potentially be repressed by several miRNAs (either individually or in combination) and one miRNA can potentially repress the translation of several genes. In Chapter 11 you saw that the organization of bacterial genes into operons permitted the coordinate regulation of genes that contributed to a single trait, such as the ability to utilize the sugar lactose. Given that most eukaryotic genes are not organized into operons, it has been suggested that post-transcriptional regulation of several genes by one miRNA affords higher organisms the ability to coordinate the expression of their genes.