Talk:MicroRNA

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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 1 RNA interference 2 suggested paragraphs 3 efficient processing of miRNA by Drosha 4 siRNA sequence selection web tools

[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).