21 Large Noncoding RNAs in Mammalian Gene Dosage Regulation

Abstract

The previous chapters discussed the biology of short RNAs and the mechanisms of gene silencing by these classes of RNAs. At the other end of the spectrum are large noncoding RNAs (ncRNA), which also have a role in transcriptional regulation. The mechanisms used by long RNAs are extraordinary and unsolved. No general rules can be applied to how long ncRNAs regulate their target genes, for these RNAs are diverse and numerous. Large ncRNAs can be complementary to the genes they regulate, whereas others do not have any sequence overlap with target genes. Some act in cis, and others function in trans. In this chapter, we explore the diversity of large ncRNAs by discussing examples from X-chromosome inactivation (XCI) and genomic imprinting, both of which utilize large ncRNA genes to influence chromatin structure across large chromosomal domains.

XCI is the mammalian strategy for dosage compensation that leads to silencing of nearly all genes on one X chromosome. It is regulated by an X-linked locus known as the “X-inactivation center” (Xic), a region notable for a dearth of protein-coding genes and for a plethora of ncRNA. So far, three of the ncRNA genes have been implicated in controlling various steps of XCI. The process of genomic imprinting also controls allelic expression of large chromosomal domains. In genomic imprinting, only one of two alleles in a given cell is expressed, and which allele becomes silenced depends on its parent of origin. Many mammalian chromosomes are imprinted to some degree. Like the Xic, imprinted...