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Non–coding RNA genes and the modern RNA world

Key Points

  • Although some textbooks still discuss only three types of RNA (ribosomal RNA, transfer RNA and messenger RNA), many other non-coding RNA (ncRNA) species have been isolated anecdotally.

  • Systematic screens looking for more ncRNA genes have been undertaken recently.

  • Two large families of small nucleolar RNAs are involved in directing site-specific modifications of rRNAs and other RNAs, and the number of known genes in these families continues to grow rapidly.

  • Three recent papers describe a new large eukaryotic RNA gene family, the microRNAs — tiny 21–24-nucleotide RNAs that are probably acting as translational regulators of protein-coding mRNAs.

  • Four recent papers describe screens for new ncRNA genes in Escherichia coli, leading to the experimental confirmation of more than 30 new non-coding transcripts of as yet unknown function, and the computational prediction of many more.

  • RNA genes have been thought of as rare relics of a primordial “RNA world” that has largely been replaced by more efficient proteins. Now, though, it seems that ncRNAs might be numerous and highly adapted in their roles in modern organisms.

  • RNA is particularly well suited to the job of specific recognition of other RNAs by complementary base pairing. Evolution might favour ncRNAs instead of proteins in certain roles; for instance, as post-transcriptional regulatory molecules that interact with specific mRNAs.

Abstract

Non-coding RNA (ncRNA) genes produce functional RNA molecules rather than encoding proteins. However, almost all means of gene identification assume that genes encode proteins, so even in the era of complete genome sequences, ncRNA genes have been effectively invisible. Recently, several different systematic screens have identified a surprisingly large number of new ncRNA genes. Non-coding RNAs seem to be particularly abundant in roles that require highly specific nucleic acid recognition without complex catalysis, such as in directing post-transcriptional regulation of gene expression or in guiding RNA modifications.

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Figure 1: Diagrams of snoRNAs guiding modification to target rRNA bases.
Figure 2: Examples of proposed interactions between the Caenorhabditis elegans lin-4 microRNA and a target mRNA.
Figure 3: Three examples of microRNAs.
Figure 4: Example of an Escherichia coli riboregulator.
Figure 5: Jacob and Monod's proposal for the nature of “regulatory genes”.

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The ENCODE Project Consortium, Michael P. Snyder, … Richard M. Myers

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Acknowledgements

I thank T. Tuschl, V. Ambros, D. Bartel, S. Holbrook and C. Burge for generously sharing pre-publication results.

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DATABASES

The following terms in this article are linked online to:

LocusLink 

Dicer

dyskerin

H19

IPW

MRP

Piwi

RMRP

roX

SCA8

telomerase

XIST 

OMIM 

autosomal-dominant dyskeratosis congenita

cartilage–hair hypoplasia

Prader–Willi syndrome

spinocerebellar ataxia 8

systemic lupus erythematosus 

TAIR 

ARGONAUTE 

WormBase 

alg-1

alg-2

let-7

lin-4

lin-14

lin-28

lin-41

lin-42

RDE-1

Glossary

U RNA

Small nuclear RNA in eukaryotes. The first such RNAs to be found were rich in uridine (U), and the name stuck.

NUCLEOLUS

A highly organized nuclear organelle that is the site of ribosomal RNA processing and ribosome assembly.

RIBONUCLEASE P

A universally conserved enzyme that cleaves a leader sequence from tRNA precursors.

SIGNAL RECOGNITION PARTICLE

An RNA–protein complex involved in exporting secreted proteins from the cell.

RNA PROCESSING

A general term for the maturation of a precursor RNA; includes the processes of RNA splicing, RNA modification, RNA editing and RNA cleavage.

CAJAL BODIES

(also known as coiled bodies). Nuclear organelles of unknown function, named in honour of Ramón y Cajal.

RNA TAILING

A technique in which an artificial homopolymer sequence is enzymatically added to an RNA to facilitate molecular cloning, as opposed to relying on the presence of a natural poly-A tail.

HETEROCHRONIC MUTATION

A mutation that alters the timing of developmental events, such as the sequence of larval moults in nematodes.

SHINE/DALGARNO SEQUENCE

A consensus sequence recognized during translational initiation by Escherichia coli ribosomes.

PURIFYING SELECTION

A common form of evolutionary change in which a mutation is harmful, and therefore disappears from the population.

NEUTRAL DRIFT

The process by which DNA sequence acquires many mutations over time that have no phenotypic effect, and hence are not acted on by Darwinian selection.

POSITIVE SELECTION

A rare form of evolutionary change in which a mutation seems to be favoured because it is fixed in the population at a rate even greater than predicted by neutral drift.

NEURAL NETWORK

A popular machine learning method that is often used for automatic classification of biological sequences, based on 'training' on a set of known examples.

SM PROTEIN

An RNA-binding protein recognized by antibodies that are produced by people with certain autoimmune diseases; 'Sm' stands for 'Smith', the name of a patient.

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Eddy, S. Non–coding RNA genes and the modern RNA world . Nat Rev Genet 2, 919–929 (2001). https://doi.org/10.1038/35103511

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