It seems to be generally accepted that the passenger strand of microRNA (miR*) is typically much less abundant than the guide strand (presumably, due to higher degradation rates of the former). However, in the RNA-seq results we can see some fraction of microRNAs displaying the opposite distribution, i.e. much higher abundance of the passenger strand. I would be grateful if someone can point to any paper or other resource with current interpretation of this phenomenon.
My own ideas on this question include, for example, 1) Misclassification of mature strand (i.e. the more abundant strand is in fact a guide one, not passenger), 2) Guide strand has fast turnover and is quickly degraded as well.
Is it also possible, that both strands of the microRNA are viable and become functional miRNA that target different mRNA populations?
We have recently revised the human miRNA complement and introduced a co-mature category for miRNAs that show the very pattern you describe OR were both arms show in all samples less than 2 fold different in expression.
Article A Uniform System for the Annotation of Vertebrate microRNA G...
The idea of a "passenger strand" was common a few years ago, but it doesn't really fit with the fact that many pre-miRNAs are processed to produce two miRNAs (which can be of differing levels).
miRBase stopped referring to stands as passenger or miR* back in 2011, and it now refers to each [potential] miRNA product as -3p or -5p depending on which arm of the pre-miRNA they come from. See: http://www.mirbase.org/blog/2011/04/whats-in-a-name/
MiRBase indeed has discontinued referring to strands. In our latest paper we show, however, that mature products show a significantly different tempo and mode of sequence evolution than their star/passenger/* counterparts which clearly supports functional constraints that justify and explain the widely and often observed bias towards mature products in sequencing datasets
Vasily,
"For many microRNA precursors the "passenger strand" does not make it into the RISC and is not used. For others, for example miR-9 and miR-21, it seems that both strands are used and that the precursor is used to produce 2 (very different) microRNAs." (Thomas Andl, from the response to the question of Yunyun Guo on the ResearhGate).
Hence, it depends. The miR-21-3p can play a dominant role in some processes (see the attached files).
Thank you so much everybody for this valuable input! I will probably add some more comments after carefully reading materials you referred.
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