The Meaning of the Microprocessor: Accounting for Evolution of Structural-Functional Novelty in the Canonical microRNA Biogenesis Pathway
It is standard to identify and compare genomic or mRNA sequence of the Drosha and Pasha genes subsidiary to detection and identification of novel microRNAs in newly sequenced taxa or review of previous deep sequencing data. Drosha and Pasha are the key, conserved gene members of the ‘microprocessor’ protein complex which facilitates nuclear nuclear-localized, pri- to pre-miRNA processing miRNAs of the canonical eumetazoan complement. Because of the necessity of the microprocessor
... e microprocessor for production of canonical eumetazoan miRNA, the detection of both (1) bona fide microRNAs and (2) presence of Drosha/Pasha orthologs (or homologs) is often presented as sufficient to represent a functional canonical eumetazoan microRNA biogenesis pathway. However, the functional role of the Drosha and Pasha homologs is not commonly experimentally investigated in non-model taxa, and therefore the assumption is not necessarily valid. Differentiation of ‘bona fide miRNAs’, opposed to ‘non-bona fide’ small RNAs of similar size, are also necessary for miRNA sequencing projects. Recent rubrics are based on structural and sequence elements of the miRNAs themselves, however these inclusion criteria include paraphyletic groupings of miRNAs, for example eumetazoan miRNAs and streptophyte (green plant) miRNAs which are not produced by the Drosha/Pasha microprocessor mechanism. Therefore, a dichotomy exists between the structural definitions for miRNAs and understanding of the evolutionarily conserved function of the microprocessor and its components. In this article, I review literature in the context of this topic and discuss philosophical ramifications for understanding the importance of the microprocessor in understanding the evolutionary and molecular origins of miRNA.