ncRNAs

Non-coding RNA (ncRNA) genes produce functional RNA molecules rather than encoding proteins.

Non-coding RNAs refers to transcripts expressed and processed in the nucleus much like any protein coding gene, but lacking an open reading frame and often transcribed antisense to bona fide protein coding genes.

In mammals, these types of transcripts are highly coincident with allele-specific silencing of imprinted genes and have a proven role in dosage compensation via X-inactivation.

Mechanisms such as RNA interference may have deep phylogenetic roots, but their relevance to imprinting and X-inactivation in mammals has not been proven.

The remarkable diversity of non-coding transcription associated with parent-of-origin directed gene silencing hints at an equally diverse assortment of mechanisms.

Functions

The significance of noncoding RNAs in processes such as chromatin dynamics and gene silencing has received increased attention over the last years, especially following the unmasking of the large group of small regulatory microRNAs.

Noncoding RNAs have long been known to regulate fundamental processes, such as the function of Xist in the initiation of X-chromosome inactivation; also, processes such as Polycomb-mediated silencing and the association of HP1 to chromatin have been reported to involve an RNA moiety.

In addition, noncoding antisense RNAs are involved in processes of imprinting, suggesting a pattern in which antisense RNA can induce transcriptional silencing as a means of gene regulation in normal and disease cells.

This theory was recently supported for the -globin gene from a patient carrying a deletion that juxtaposes the highly expressed LUC7L gene in antisense to beta-globin.

Importantly, the antisense RNA induces transcriptional silencing of the -globin gene associated with methylation of the CpG island at the beta-globin gene. Also, data from fission yeast implicate the RNAi machinery in the initiation and maintenance of heterochromatin.

The functions of the vast majority of non-coding RNA transcripts remain elusive. Most act as RNA guides for protein enzymes. Several non-coding RNAs (ncRNAs) regulate eukaryotic mRNA transcription. ncRNAs typically function as ribonucleoprotein (RNP) complexes and not as naked RNAs.

Non-coding RNAs (ncRNAs) with gene regulatory functions are starting to be seen as a common feature of mammalian gene regulation with the discovery that most of the transcriptome is ncRNA. The prototype has long been the Xist ncRNA, which induces X-chromosome inactivation in female cells.

Xist-like model is only one of many possible solutions and that imprinted ncRNAs could provide the better model for understanding the function of the new class of ncRNAs associated with non-imprinted mammalian genes. It creates a new paradigm: the silencing of imprinted gene clusters by long ncRNAs.

Embryogenesis

Non-coding RNAs (ncRNAs) are emerging as key regulators of embryogenesis. They control embryonic gene expression by several means, ranging from microRNA-induced degradation of mRNAs to long ncRNA-mediated modification of chromatin.

Many aspects of embryogenesis seem to be controlled by ncRNAs, including the maternal-zygotic transition, the maintenance of pluripotency, the patterning of the body axes, the specification and differentiation of cell types and the morphogenesis of organs.

There are two emerging themes for ncRNA function: promoting developmental transitions and maintaining developmental states. These examples highlight the roles of ncRNAs in ensuring a robust commitment to one of two possible cell fates.

See also

 RNA-guided proteins
 ncRNA transcriptional regulators
 small RNAs

• small nuclear RNAs
• small nucleolar RNAs

References

 Non-coding RNAs as regulators of embryogenesis. Pauli A, Rinn JL, Schier AF. Nat Rev Genet. 2011 Feb;12(2):136-49. PMID: 21245830

 Matera AG, Terns RM, Terns MP. Non-coding RNAs: lessons from the small nuclear and small nucleolar RNAs. Nat Rev Mol Cell Biol. 2007 Mar;8(3):209-20. PMID: 17318225

 Goodrich JA, Kugel JF. Non-coding-RNA regulators of RNA polymerase II transcription. Nat Rev Mol Cell Biol. 2006 Aug;7(8):612-6. Epub 2006 May 24. PMID: 16723972

 Huttenhofer A, Schattner P. The principles of guiding by RNA: chimeric RNA-protein enzymes. Nat Rev Genet. 2006 Jun;7(6):475-82. PMID: 16622413

References

 Pang KC, Frith MC, Mattick JS. Rapid evolution of noncoding RNAs: lack of conservation does not mean lack of function. Trends Genet. 2006 Jan;22(1):1-5. PMID: 16290135

 Huttenhofer A, Schattner P, Polacek N. Non-coding RNAs: hope or hype? Trends Genet. 2005 May;21(5):289-97. PMID: 15851066

 O’Neill MJ. The influence of non-coding RNAs on allele-specific gene expression in mammals. Hum Mol Genet. 2005 Apr 15;14 Spec No 1:R113-20. PMID: 15809263