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translation of cleaved miRNA targets


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#1 andrea massimo

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Posted 14 August 2009 - 07:03 AM

Can mRNA 3' or 5' fragments deriving from miRNA-mediated cleavage be translated into truncated proteins?

Edited by andrea massimo, 14 August 2009 - 01:08 PM.


#2 Jon Moulton

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Posted 14 August 2009 - 01:53 PM

Here is a guess: Yes, but it is less likely that translation will initiate. The mRNA normally forms a circle through interactions of factors bound to the 3' and 5' ends. This association favors initiation of translation. With the mRNA cleaved, the 3' and 5' ends would diffuse unconstrained and be less likely to be close enough to associate and initiate translation.

Does anyone have real information about this?
Jon D. Moulton
Gene Tools, LLC
www.gene-tools.com

#3 housemusicanl

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Posted 20 August 2009 - 12:29 AM

I recently read a review where the authors speculated on this sort of thing towards the end

- http://www.nature.co...bs/nrm2619.html

Basically, since repression is sufficient for 100% target clearance in many cases then cleavage of transcripts may serve some function - given that the fragments themselves are biologically stable. In other contexts too spliced transcripts can be a source of ncRNAs - piRNAs, tasiRNAs.
As examples they mentioned cis-acting methylation of PHB after miR-165 binding in A.thaliana, restoration of protein activity in oskar mutant of D.melanogaster by the 3'UTR alone, and ncRNA influence on HOX genes in mammals.
They also described a scenario where transcript fragments could 'titrate' activator proteins that would have bound to the mRNA - serving to increase repression further.

The rest of the review is very good as well

#4 andrea massimo

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Posted 25 August 2009 - 02:12 AM

Thank you for your comments. mRNA 3' and 5' modifications are usually required for translation. Yet, there are exceptions, and on the other hand it is not so sure that they are missing in miRNA mediated degradation fragments. The review by brodersen and voinnet is very interesting.
Also interesting is the report by Thoma et al, molecular cell, 2001. http://www.cell.com/...097276501003641
The authors showed that in human celles mRNA 3' degradation fragments derived by DNA oligo pairing and subsequent cleavage were stable and translated into truncated proteins. A fraction of the fragments were found to be uncapped, but the authors didn't rule out that some of them could be re-capped after cleavage.




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