miR-634 is a Pol III-dependent intronic microRNA regulating alternative-polyadenylated isoforms of its host gene PRKCA.


BACKGROUND The protein kinase C alpha (PRKCA) gene, coding for a Th17-cell-selective kinase, shows a complex splicing pattern, with at least 2 stable alternative transcripts characterized by an alternative upstream polyadenylation site. Polymorphisms in this gene were associated with several conditions, including multiple sclerosis, asthma, schizophrenia, and cancer. The presence of a microRNA (miRNA), i.e. miR-634, within intron 15 of the PRKCA gene, suggests the intriguing possibility that this miRNA might play a role in the susceptibility to these pathologies. METHODS Here, we characterized miR-634 expression profile and searched for its putative targets using a combination of RT-PCR and gene reporter assays. RESULTS The quantitative analysis of PRKCA and miR-634 transcripts in a panel of human tissues and cell lines revealed discordant expression profiles, suggesting the presence of an independent miR-634 promoter and/or a possible direct role of miR-634 in modulating PRKCA expression. Functional studies demonstrated the existence of a miRNA-specific promoter, which was shown to be Pol-III-dependent. Furthermore, transfection experiments showed that miR-634 is able to target its host gene by specifically down-regulating the shorter alternative-polyadenylated isoforms. CONCLUSIONS MiR-634 is a Pol III-dependent intronic miRNA, which could target its host gene through a "first-order" negative feedback. GENERAL SIGNIFICANCE MiR-634 is one of the few characterized examples of Pol-III-dependent intronic miRNAs. Its independent transcription from the host gene suggests caution in using expression profiles of host genes as proxies for the expression of the corresponding intronic miRNAs.

DOI: 10.1016/j.bbagen.2017.02.016

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@article{Paraboschi2017miR634IA, title={miR-634 is a Pol III-dependent intronic microRNA regulating alternative-polyadenylated isoforms of its host gene PRKCA.}, author={Elvezia Maria Paraboschi and Giulia Cardamone and Valeria Rimoldi and Stefano Duga and Giulia Sold{\`a} and Rosanna Asselta}, journal={Biochimica et biophysica acta}, year={2017}, volume={1861 5 Pt A}, pages={1046-1056} }