Long Non-Coding RNAs

On Ørom and Shiekhattar, 2011 in Curr Opin Genet Dev

Approximately 1.5 % of our genome is transcribed to protein-coding mRNA.  The existence of noncoding RNAs such as ribosomal and transfer RNAs as well as small nucleolar RNAs has been known for a long while now. More recently the RNA interference machinery and the associated microRNAs have been associated with important functions.  Now thanks to next-gen sequencing, it is becoming clear that remainder of the genome is not all junk but could code for long noncoding RNAs (long ncRNA or lncRNA).

Ørom and Shiekhattar give a review of the current research on these RNAs and they elaborate on the link with enhancers (Ørom and Shiekhattar, 2011). The authors note that the current understanding on long ncRNAs is very primitive. lncRNAs are very heterogenous which makes it hard to classify and decode the information they carry. Their distinctive property is that they lack protein-coding ORFs and they are longer than small regulatory RNAs .

Some of the complexities include changes in size and copy number (average length ~1kb).  Specific studies such as the ones on the HOX gene cluster and the beta-globin locus show that some lncRNAs can have regulatory functions on the expression of nearby protein coding genes. Some of the studied lncRNAs act in cis while others in trans which adds to the heterogeneity. In addition some of the lncRNAs have features of protein coding mRNAs such as polyAdenylation and splicing.

In both mouse and human cells, some lncRNAs are associated with enhancers. The elucidation of histone marks around the active enhancers supports this hypothesis. Although correlative analyses implicate these lncRNAs in the positive regulation of nearby genes, a mechanistic understanding is missing. What kind of code or information do lncRNAs have, to mediate their functions? This seems to be the foremost challange  in the field.  Their hetreogeneity and the possibility of multiple mechanisms granted, one hypothesis suggests that 3-dimensional structures of lncRNAs might interact with transcription factors and function to alter gene expression. However, published studies are not enough to reach a conclusion about this theory, yet.

Ulf Andersson Ørom, Ramin Shiekhattar, Long non-coding RNAs and enhancers, Current Opinion in Genetics & Development, Volume 21, Issue 2, April 2011, Pages 194-198, ISSN 0959-437X, 10.1016/j.gde.2011.01.020.