MiRNA

From Free net encyclopedia

(Redirected from Micro RNA)

In genetics, a miRNA (micro-RNA) is a form of single-stranded RNA which is typically 20-25 nucleotides long, and is thought to regulate the expression of other genes. miRNAs are RNA genes which are transcribed from DNA, but are not translated into protein. The DNA sequence that codes for an miRNA gene is longer than the miRNA. This DNA sequence includes the miRNA sequence and an approximate reverse complement. When this DNA sequence is transcribed into a single-stranded RNA molecule, the miRNA sequence and its reverse-complement base pair to form a double stranded RNA hairpin loop; this forms a primary miRNA structure (pri-miRNA). In animals, the nuclear enzyme Drosha cleaves the base of the hairpin to form pre-miRNA. The pre-miRNA molecule is then actively transported out of the nucleus into the cytoplasm by Exportin 5, a carrier protein. The Dicer enzyme then cuts 20-25 nucleotides from the base of the hairpin to release the mature miRNA. In plants, which lack Drosha homologues, pri- and pre-miRNA processing by Dicer probably takes place in the nucleus, and mature miRNA duplexes are exported to the cytosol by Exportin 5.

The function of miRNAs appears to be in gene regulation. For that purpose, a miRNA is complementary to a part of one or more messenger RNAs (mRNAs). Animal miRNAs are usually complementary to a site in the 3' UTR whereas plant miRNAs are usually complementary to coding regions of mRNAs. The annealing of the miRNA to the mRNA then inhibits protein translation, but sometimes facilitates cleavage of the mRNA. This is thought to be the primary mode of action of plant miRNAs. In such cases, the formation of the double-stranded RNA through the binding of the miRNA triggers the degradation of the mRNA transcript through a process similar to RNA interference (RNAi), though in other cases it is believed that the miRNA complex blocks the protein translation machinery or otherwise prevents protein translation without causing the mRNA to be degraded. miRNAs may also target methylation of genomic sites which correspond to targeted mRNAs. miRNAs function in association with a complement of proteins collectively termed the miRNP.

This effect was first described for the worm Caenorhabditis elegans in 1993 by R. C. Lee of Harvard University. As of 2002, miRNAs have been confirmed in various plants and animals, including C. elegans, human and the plant Arabidopsis thaliana. Genes have been found in bacteria that are similar in the sense that they control mRNA abundance or translation by binding an mRNA by base pairing, however they are not generally considered to be miRNAs because the Dicer enzyme is not involved.

The term miRNA was first introduced in a set of three articles in Science (26 October 2001)<ref>{{cite journal |url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11679654 |title=Molecular biology. Glimpses of a tiny RNA world. |last=Ruvkun |first= G. |journal=Science |year=2001 |month=Oct 26 |volume=294 |issue=5543 |pages=797-9 |id=PMID: 11679654}}</ref>

In plants, similar RNA species termed short-interfering RNAs siRNAs are used to prevent the transcription of viral RNA. While this siRNA is double-stranded, the mechanism seems to be closely related to that of miRNA, especially taking the hairpin structures into account. siRNAs are also used to regulate cellular genes, as miRNAs do.

The activity of an miRNA can be experimentally blocked using a locked nucleic acid oligo, a Morpholino oligo<ref>{{cite journal |url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15585662&query_hl=3 |journal=Nucleic Acids Res. |year=2004 |month=Dec 7 |volume=32 |issue=21 |pages=6284-91 |title=Substrate requirements for let-7 function in the developing zebrafish embryo |last=Kloosterman |first=WP |id=PMID: 15585662 |coauthors=Wienholds E, Ketting RF, Plasterk RH}}</ref> or a 2'-O-methyl RNA oligo. <ref>{{cite journal |url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14970398&query_hl=13&itool=pubmed_docsum |journal=RNA |year=2004 |month=Mar |volume=10 |issue=3 |pages=544-50 |title=Sequence-specific inhibition of microRNA- and siRNA-induced RNA silencing |last=Meister |first=G |coauthors=Landthaler M, Dorsett Y, Tuschl T |id=PMID: 14970398}}</ref>Most efficient methods for miRNA detection are based on oligonucleotides modified with locked nucleic acids.<ref>{{cite journal |url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16369549&query_hl=1&itool=pubmed_docsum |journal=Nat Methods |year=2006 |month=Jan |voluime=3 |issue=1 |pages=27-9 |title=In situ detection of miRNAs in animal embryos using LNA-modified oligonucleotide probes |last=Kloosterman |first=WP |coauthors=Wienholds E, de Bruijn E, Kauppinen S, Plasterk RH |id=PMID: 16369549}}</ref>

1 miRNA and cancer
2 References
3 See also
4 External links

[edit]

miRNA and cancer

miRNA has been found to have links with some types of cancer.

A study of mice altered to produce excess c-myc — a protein implicated in several cancers — shows that miRNA has an effect on the development of cancer. Mice that were engineered to produce a surplus of types of miRNA found in lymphoma cells developed the disease within 50 days and died two weeks later. In contrast, mice without the surplus miRNA lived over 100 days.<ref>Template:Cite journal</ref>

Another study found that two types of miRNA inhibit the E2F1 protein, which regulates cell proliferation. miRNA appears to bind to messenger RNA before it can be translated to proteins that switch genes on and off.<ref>Template:Cite journal</ref>

By measuring activity among 217 genes encoding miRNA, patterns of gene activity that can distinguish types of cancers can be discerned. miRNA signatures may enable classification of cancer. This will allow doctors to determine the original tissue type which spawned a cancer and to be able to target a treatment course based on the original tissue type. miRNA profiling has already been able to determine whether patients with chronic lymphocytic leukemia had slow growing or aggressive forms of the cancer.<ref>Template:Cite journal</ref>

[edit]

References

This paper defines miRNA and proposes guidelines to follow in classifying RNA genes as miRNA: Template:Cite journal
This paper discusses the processes that miRNA and siRNAs are involved in, in the context of 2 articles in the same issue of the journal Science: Template:Cite journal
This paper describes the discovery of lin-4, the first miRNA to be discovered (editor's note: in fact, no Wikipedia editor has yet read this paper, only made inferences from a citation): Template:Cite journal

[edit]