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Non-coding RNA

A non-coding RNA (ncRNA) is any RNA molecule that is not translated into a protein. A previously used synonym, particularly with bacteria, was small RNA (sRNA). However, some ncRNAs are very large (e.g. Xist). Less-frequently used synonyms are non-protein-coding RNA (npcRNA), non-messenger RNA (nmRNA), small non-messenger RNA (snmRNA), or functional RNA (fRNA). The DNA sequence from which a non-coding RNA is transcribed as the end product is often called an RNA gene or non-coding RNA gene (see gene).

Non-coding RNA genes include transfer RNA (tRNA) and ribosomal RNA (rRNA), small RNAs such as snoRNAs, microRNAs, siRNAs and piRNAs and lastly long ncRNAs that include examples such as Xist, Evf, Air, CTN and PINK (see here for a more complete list of ncRNAs). The number of ncRNAs encoded within the genome is unknown, however recent transcriptomic and microarray studies suggest the existence of over 30,000 long ncRNAs and at least as many small regulatory RNAs within the mouse genome alone. Since most of the newly identified ncRNAs have not been validated for their function, it is possible that the majority of them are meaningless (e.g. non-functional or truncated transcript).

One of the major findings of the 2007 ENCODE Pilot Project was that "nearly the entire genome may be represented in primary transcripts that extensively overlap and include many non-protein-coding regions.

The evaluation of ncRNA has changed radically

It was formerly believed that the main role for RNA was to code for protein, though there were the recognized exceptions of rRNA (ribosomal), and tRNA (transfer). It was assumed that any leftover ncRNA which served none of those roles must usually be mere "junk" coding. Some might conceivably be coopted later by chance in the course of evolution, but it was otherwise assumed to be useless.

There began to be signs that this was not true, e.g. with the paper by Brannan et al. (1990). Then by 2001, Mattick had claimed that in fact this applied to more than 97% of the RNA produced from DNA. (See also later works by Mattick and others.) Given this imbalance, it became clear that ncRNA must be playing other important roles; but what?

Newfound role — as "regulators" of various types

It has been becoming increasingly clear that cross-interactions between genes play a crucial role, and the importance of ncRNA for this task is explored in some detail in the table below. Rather less obvious is ncRNA's postulated role in how the brain deals with non-trivial thought processes, as follows:

Possible role as the most basic encodings for memory and behaviour

In developing his theory of cognitive development, the late Professor Piaget based his explanations on abstract constructs called "schemes". That leaves open just what these schemes might be in physical terms, though he did briefly consider the possibility of RNA in 1967. Such roles for RNA fell out of favour by about 1980 (partly because any such RNA was seen only as some sort of protein-producing adjunct to synaptic change). Meanwhile, based on some work from the 1970s, Traill (2005) argued that some sort of linear coding must underlie memory (at least for advanced thinking), and that RNA is the only plausible candidate.

Such an action-or-memory-encoding role need not conflict with the aforementioned "regulator" role. In fact "thought" itself might be seen as a special case of internal regulation. (Moreover this connection was perhaps already implied in the 1950s by Ross Ashby when he argued that recursive elaborations to a simple homeostat could yield a brainlike system..)

Distinction between functional RNA (fRNA) and ncRNA

The term ncRNA has been used, in addition to its above definition, to describe regions of mRNA that are functional at the RNA level, i.e. they have a biological function other than coding for protein even though they are on a protein-coding mRNA, for example riboswitches and the SECIS element.

They may even overlap with protein-coding sequence and are thus dual-functional: at the RNA level and at the protein level (e.g. SgrS RNA and RNAIII). However, these conflict with the Sequence Ontology's definition of ncRNA, which requires that a RNA does not contain any protein-coding sequence in order to be labeled ncRNA.

Several publications have started using the term functional RNA (fRNA), as opposed to ncRNA, to describe regions functional at the RNA level that may or may not be stand-alone RNA transcripts. Therefore, every ncRNA is a fRNA, but there exist fRNA (such as riboswitches, SECIS elements, and other cis-regulatory regions) that are not ncRNA. Yet the term fRNA could also include mRNA as this is RNA coding for protein and hence is functional. Additionally artificially evolved RNAs also fall under the fRNA umbrella term. Some publications state that the terms ncRNA and fRNA are nearly synonymous.

Untranslated regions of mRNAs

Messenger RNA (mRNA) contains non-coding regions at its ends (called UTRs) which include riboswitches and the SECIS element. Many of the functional elements in UTRs are cis-regulatory elements.

See also

References

External links

  • Comprehensive database of mammalian ncRNAs
  • The Rfam Database A curated list of hundreds of families of related ncRNAs. Each family includes a multiple alignment of known members, and predicted homologs in a large genome database. The definition of "family" is a pragmatic one, the goal being to lead to high-quality annotations. Thus, some families are quite broad (e.g. all tRNAs are in one family, as of 2004), while some families are quite narrow (e.g. there are many microRNA families, one for each type).
  • ncRNA databaseNONCODE is a brand-new database of all kinds of noncoding RNAs (except tRNAs and rRNAs).

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