Talk:MicroRNA
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The first sentance states that miRNAs are single stranded molecules. My understanding was that miRNAs were short, double stranded RNAs that were formed after processing of single stranded RNA precursors existing in a stem loop conformation. Please clarify. Thewookie55 20:36, 5 July 2007 (UTC)
- They are indeed double-stranded for a short while during their biogenesis but one strand (the "passenger") is discarded during maturation. The active form is single-stranded so that it is free to hybridise to the target mRNA. Same for siRNAs by the way. Tospo 09:37, 30 October 2007 (UTC)
The title is wrong. It should be either "miRNA" or "micro-RNA". The first letter should not be capitalized. AdamRetchless 23:11, 8 Apr 2004 (UTC)
In the literature it is capitalized only at the beginning of a title or sentence and it is mostly written without a space or hyphen ("microRNA" or "miRNA"). Mateo 23:21, 21 June 2006 (UTC)
Any idea as to why the Microprocessor complex proteins are named Drosha and Pasha? Pasha is a military leader, and Drosha is flag. Any alternate possibilities? ValaRaukar 10:00, 31 July 2006 (UTC)
- Pasha could also be a Russian soft variant of the name "Pavel" (Paul), Drosha = Andrusha = Andrey (Andrew). CopperKettle 04:51, 28 February 2007 (UTC)
shRNA and miRNA action differs significantly. While complementarity of miRNA to the target mRNA may be 100%, only specific positions, mostly at 5'-end, should be precise. shRNA on another hand depends on absolute complementarity to work.
Would information on pol II and III promoters be relevant?
Yeah, miRNAs must be refered to as a subclass of siRNAs, not something different.
There is no mention of piRNA or piwi-interacting RNA which are important in germline development.GetAgrippa 01:29, 12 September 2006 (UTC)
- I'm not familiar with piRNAs, but I don't think they're microRNAs (even if they're small). I think microRNAs are very small RNAs (~22 nucs) that are processed by the dicer enzyme and are antisense to mRNAs. Perhaps another article should be started on piRNAs? Zashaw 23:25, 12 September 2006 (UTC)
Your are correct that they are not miRNA. They are 29-30 nucleotides so they are longer than most micro RNA's, however they are small RNA's. Transcriptional gene silencing (piRNA mediated) usually represses gene expression by altering chromatin structure, unlike the miRNA and dicer enzyme. There is already mention of siRNA and then there is repeat associated small interference RNA, perhaps we should have an article called small RNA's and entertain all of them.GetAgrippa 21:00, 13 September 2006 (UTC)
- I've learned something today. (Now I can goof off till tomorrow ;-) There's already an article Non-coding RNA, which I consider a synonym for small RNA (although "small" in this case means less than say a couple hundred nucs). What I would propose is a separate article on piRNAs, which would be linked from Non-coding RNA, and probably microRNA. Or maybe if there's not that much info on piRNAs, then just a paragraph in the Non-coding RNA article. Seem right? Zashaw 00:16, 14 September 2006 (UTC)
- I didn't know of the article either Zashaw. It could be condensed into a sentence or two for a short concise description. It will fit nicely in the non-coding RNA article (which is shaping up nicely-most excellent) after I quickly gave it a look see. Great call! I have a Science review article talking about piRNA, miRNA, etc. that I could use for a concise sentence or two. It may need its own stub for more detail, but the noncoding article is a great place to tie it all together. GetAgrippa 05:07, 15 September 2006 (UTC)
I would strongly object to the term 'non-coding RNA' being applied to describe group of si-, mi-, sh-, pi- and asRNA. I think that a term 'RNAi molecules' (=interfering) would describe this group much better for several reasons. First of all, they all 'interfere' with target gene expression either transcriptionally or translationally (with RNA degradaion been somewhere inbetween). Second, their interference depends on (partial) complementarity to the target mRNA or target DNA. There are some other properties which can be used to pull them together but we should remember several other classes of 'non-coding' RNAs, namely ribosomal and transport RNA. In my opinion only RNAs proceeded by Dicer and afterwards incorporated into RISK should be included in this article or it becomes too big and vague. My two eurocents.Iralets 20:19, 25 September 2006 (UTC)Igor
- If we have enough content on these RNAs, we should put them in a more specific article. I haven't been following the literature enough to say what the article should be called. However, at the moment, the non-coding RNA article seems logical, because (1) we only have a small amount of information on the sh-, pi- and asRNA, and (2) these _are_ non-coding RNAs. Regardless, an article on Dicer and/or the RISC seems worthwhile, no matter where we discuss things. Zashaw 21:51, 25 September 2006 (UTC)
Last issue of Nature Methods has a huge chunk allocated to put together all that is known in this field (http://www.nature.com/nmeth/journal/v3/n9/index.html ). I can't agree that we don't know enough to put an article together. Since I'm new to Wiki I don't know how deep/specialized an article should be but general design based on energy distribution for preferable incorporation into RISC is rather widespread.Iralets 07:05, 26 September 2006 (UTC)
I've just read this article : Hall, T.M. Structure and functions of argonaute proteins. "Structure" , 2005 Oct;13(10):1403-8. PMID: 16216572 I think that it gives pretty good insight of how RISC complex recognize target mRNA. Iralets 14:52, 3 October 2006 (UTC)
Iralets why don't you start a stub for interference RNA's. You can either write it or at least suggest a list of topics to address-Dicer, piwi,etc. Make it as detailed as you like, because laypeople will edit to a suitable encyclopedia level. Some articles are very specific and detailed depending on the topic. There are a number of good editors who can write and get it moving. Just contribute suggestions in Talk or write paragraphs. This is a collaborative effort so there are plenty of people who will keep it going. I have been amazed at the progress in "the nucleus" article in a short period of time from the collaborative process. There are a number of molecular biologist who also seek and contribute to similar articles, and scientist from other fields and laypeople often make significant contributions. The Wiki can be an incredibly productive process, but there is a lot of give and take at times. GetAgrippa 03:47, 7 October 2006 (UTC)
Contents |
[edit] RNA interference
There is already an article for RNA interference. GetAgrippa 20:09, 7 October 2006 (UTC)
[edit] suggested paragraphs
I don't know how to use Wiki's tools, please forgive me for little bit inconsistence writing:
"miRNA can be located in different parts of genome. Many miRNAs are found in non-coding regions, like the first identified lin-4 and let-7. On another hand, miRNA can be found in the coding region for the specific protein but encoded in antisence direction. In the later case this miRNA usually silences expression of the protein in the sense direction. Last class of miRNAs, based on their coding location, is intronic miRNAs. Intronic miRNA are located in intronic regions of genes. Although both 3'UTR and 5'UTR can be considered intrones, processing of intronic miRNA located in in-frame intrones varies significantly. Intronic miRNAs have two feature which define their placement into separate group: first, they share the same promoter as a target gene, and second, they must be spliced out of the transcript of such encoded genes befor further processing into mature miRNA."
"It is still disputable if intronic miRNA are processed by Drosha after their respective introne is spliced out. Another alternative could be further processing by splaceosomal components before it is transported out of nucleus. Intronic miRNAs are transported out into cytoplasm where they are cut by Dicer."
Previous two paragraphs are based on Intronic MicroRNA (miRNA), Lin et al.,PMID: 17057362 [PubMed - in process].
"miRNA-mediated post-transcriptional silencing could be achived in two ways. One way is similar to shRNA mechanism when target mRNA is degraded, and another way to achieve translational silencing is to form miRNA-protein-mRNA complex uncapable of binding to ribosomes."
Later I'll add a paragraph or two about Drosha processing and thermodinamical properties of RNA plus folding prerequisites for optimal cleavage by Drosha. I would be really greatful if somebody with deeper understanding of termodinamic properties of nucleic acids would step in and write this part.
Viral vectors is another great tool for gene silencing and a lot of groups now use viral vector delivery of miRNA. Iralets 17:14, 27 November 2006 (UTC)
anyone here involved in developmental studies? I saw several publications about distribution of miRNAs during development using LNA mediated in situ which are great but since I know almost nothing in the field of developmental biology... Iralets 17:20, 27 November 2006 (UTC)
[edit] efficient processing of miRNA by Drosha
Following paragraphs are based on two articles (plus my attempt to compile these findings): Han, J. et al. Molecular Basis for the Recognition of Primary microRNAs by the Drosha-DGCR8 Complex. Cell, 125, 887-901.
Zeng, Y., et al. Efficient Processing of Primary microRNA Hairpins by Drosha Requires Flanking Nonstructured RNA Sequences. J. Biol. Chem., 280 (30), 27595-27603
\\ Zeng et al. have shown that efficient processing of pre-miRNA by Drosha requires presence of extended single-stranded RNA on both 3'- and 5'-ends of hairpin molecule. They demonstrated that these motives could be of different composition while their length is of high importance if processing is to take place at all. Their findings were confirmed in another work by Han et al. Using bioinformatical tools Han et al. analysed folding of 321 human and 68 fly pri-miRNAs. 280 human and 55 fly pri-miRNAs were selected for further study, excluding those molecules which folding showed presence of multiple loops. All human and fly pri-miRNA contained very similar structural regions, which authors called 'basal segments', 'lower stem', 'upper stem' and 'terminal loop'. Based on the encoding position of miRNA, i.e. in the 5'-strand (5'-donors) or 3'-strand (3'-donors), thermodinamical profiles of pri-miRNA was determined. Following experiments have shown that Drosha complex cleaves RNA molecule ~2 helical turns away from the terminal loop and ~1 turn away from basal segments. In most analysed molecules this region contain unpaired nucleotides and deltaG [this triangular letter] is relatively high compared to lower and upper stem regions.
Most pre-miRNAs don't have perfect double-stranded RNA (dsRNA) structure toppled by a terminal loop. There are few possible explanations for such selectivity. One could be that dsRNAs longer then 11 base pairs activate interferon response and anti-viral machinery in the cell. Another plausible explanation could be that thermodinamical profile of pre-miRNA determines which strand will be incorporated into Dicer complex. Indeed, aforementioned study by Han et al. demonstrated very clear similarities between pri-miRNAs encoded in respective (5'- or 3'-) strands. \\
There were some works showing that dsRNAs with blunt ends are indeed strong inflammatory agents and the longer they are, the stronger is response.Iralets 13:55, 6 December 2006 (UTC)
[edit] siRNA sequence selection web tools
From Pei, Y. and Tuschl, T. On the art of identifying effective and specific siRNAs. Nature Meth., 3(9):670-676.
siDESIGN http://www.dharmacon.com/
RNAi Designer: http://rnaidesigner.invitrogen.com/
BIOPRDsi: http://www.biopredsi.org
Whitehead siRNA Selection server: http://jura.wi.mit.edu/bioc/siRNA
siDE: http://side.bioinfo.ochoa.fib.es/
siSearch: http://sisearch.cgb.ki.se/
Sirna: http://sfold.wadsworth.org/sirna.pl
siRNA design software: http://www.cs.hku.hk/~sirna
These programs can be used for designing artificial siRNA. —The preceding unsigned comment was added by Iralets (talk • contribs) 14:32, 6 December 2006 (UTC).
[edit] miR-155 section
The section on miR-155 seems too long for this general page on microRNAs. I would suggest that this material is moved to a new page specific for that microRNA. It is probably worth noting that miR-155 is the first one to be knocked out, but perhaps not much more than that. Alexbateman 13:29, 14 May 2007 (UTC)
[edit] Viral microRNAs
There is no mention of viruses encoding microRNAs which should be corrected as many DNA viruses and HIV-1 retrovirus have been demonstrated to encode microRNAs in their genomes.
[edit] MicroRNA knockout mice
Although miR-155 was indeed one of the first microRNAs to be knocked out in mice, it was preceded by the miR-1-2 knockout mouse (published April 20, 2007 in Cell, with Deepak Srivastava as corresponding author), which displays cardiac defects.
It should also be noted that the miR-155 knockout was described in two separate papers in the same issue of Science (April 27, 2007, with Klaus Rejewsky and Martin Turner/Allan Bradley as the respective corresponding authors).
[edit] Copyright infringement
I removed this text as a copyright infringement. However, it is sourced and reasonably important, so if someone wants, they can rewrite it.-Wafulz 17:15, 7 August 2007 (UTC)
[edit] =General notes
This entire article needs a revamp, there are several issues, mainly in the accuracy of the information provided/or the understanding taken therefrom. I have just completed a PhD solely on miRNAs and would be willing to incorporate accurate, thoughtful information on the topic. Just to clarify one of the earlier Discussion points, miRNAs are not a subclass of siRNAs!!! They are completely different. The main point to consider is that in mammals, endogenous (generated by the organism itself)siRNAs have not been discovered, but they are present in plants (there is also a dire need to discuss the different classes of siRNA that are present in plants and their inherent differences). Importantly, miRNAs are produced endogenously in mammals and plants, and now constitute the largest class of posttranscriptional gene regulators. miRNAs use miRISC and siRNAs use siRISC, the absolute components of these complexes are not 100% clarified, and some particular miRNAs are thought to utilise additional factors, although the complexes are typically similar. Except for a couple of rare examples, in which a miRNA causes cleavage of a mRNA, miRNAs only bind with partial complementarity to the target, and direct translational repression and or deadenylation of mRNA. The miRNA seed region (nucleotides 2-8) from the 5' end of the miRNA binds to the mRNA target. For a mRNA to be a predicted target of the miRNA, several criteria have to be considered. Besides the obvious seed region match (2-8nt) (although doesn't have to be perfect), the miRNA should be able to access the 3'UTR of the mRNA (i.e the target site must meet strict thermodynamic criteria to be considered, although it might have a perfect seed match)
One more point, Pasha was named so for Partner of Drosha. As simple as that, there is no conspiracy. Also Pasha was first identified in flies by a yeast two hybrid screen as CG1800, and only termed Pasha after another group realised that it was homologous to DGCR8 (DiGeorge Syndrome Critical Region gene 8) in humans. Both DGCR8 and Pasha are dsRBD (double stranded RNA binding domain) containing proteins that function in concert with Drosha to act as a specificity factor in Drosha directed cleavage of the pri-miRNA
also a mention of intragenic versus intergenic miRNAs, their transcription, regulation of their transcription etc should be considered, and also links to some of the sites that we use, such as targetscan and tarbase, and the miRNA registry. These are great sites.
I think that the article should be divided into: history, classification/nomenclature, biogenesis, function (with tables), examples of cancer related, developmentally related miRNAs, miRNAs as prognostic/diagnostic markers etc etc.
i.e do not mention siRNAs, piRNA etc and provide links to a separate article, it is easy to confuse people with these small (but very different) molecules, and this would provide clarity and prevent confusion
Also, miRNA expression analysis by means of Locked nucleic acid (LNA) whole mount in situ hybridisation [LNA WMISH] is a major breakthrough in miRNA research. Knowing the expression of a miRNA enables the researcher to identify possible candidate targets for furhter analysis. see Tuddenham et al (2006) for a good example of mouse LNA WMISH for miR-140.88.111.112.151 (talk) 20:46, 28 November 2007 (UTC)
[edit] miRNA and cancer section
(I am not a science wiz, I just like to read it, so sorry if I'm not saying things right and making too much sense!)
I read about this research that showed how this scientist was able to make cancer metastasize and then fully reverse the process by increasing the amount of just one miRNA. The link is below:
http://web.mit.edu/newsoffice/2007/cancer-link-0927.html
I think that it would be worth mentioning in the "miRNA and cancer" section. What do you guys think? —Preceding unsigned comment added by Believr4god (talk • contribs) 08:19, 2 April 2008 (UTC)
