Key result
Alternative splicing of the LAT lncRNA and Drosha silencing revealed that mdv1-miR-M6 is a 5'-tailed mirtron whose alternative splicing differentially affects the expression of other clustered miRNAs.
The viral mdv1-miR-M6 mirtron is the first described mirtron that can follow both the spliceosome and canonical Microprocessor pathways, affecting the expression of clustered miRNAs and host transcripts.
mdv1-miR-M6 is the first dual-pathway mirtron; extends miRNA biogenesis models but leaves open functional roles in viral infection.
Interplay between alternative splicing and the Microprocessor may have differential effects on the expression of intronic miRNAs organized into clusters. We used a viral model - the LAT long non-coding RNA (LAT lncRNA) of Marek's disease oncogenic herpesvirus (MDV-1), which has the mdv1-miR-M8-M6-M7-M10 cluster embedded in its first intron - to assess the impact of splicing modifications on the biogenesis of each of the miRNAs from the cluster. Drosha silencing and alternative splicing of an extended exon 2 of the LAT lncRNA from a newly identified 3' splice site (SS) at the end of the second miRNA of the cluster showed that mdv1-miR-M6 was a 5'-tailed mirtron. We have thus identified the first 5'-tailed mirtron within a cluster of miRNAs for which alternative splicing is directly associated with differential expression of the other miRNAs of the cluster, with an increase in intronic mdv1-miR-M8 expression and a decrease in expression of the exonic mdv1-miR-M7, and indirectly associated with regulation of the host transcript. According to the alternative 3SS used for the host intron splicing, the mdv1-miR-M6 is processed as a mirtron by the spliceosome, dispatching the other miRNAs of the cluster into intron and exon, or as a canonical miRNA by the Microprocessor complex. The viral mdv1-miR-M6 mirtron is the first mirtron described that can also follow the canonical pathway.
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Rasschaert et al. (2016) studied Marek's disease oncogenic herpesvirus (MDV-1) infection model. Drosha silencing and alternative splicing of LAT lncRNA was evaluated on Biogenesis and expression of miRNAs from the mdv1-miR-M8-M6-M7-M10 cluster. Alternative splicing of the LAT lncRNA and Drosha silencing revealed that mdv1-miR-M6 is a 5'-tailed mirtron whose alternative splicing differentially affects the expression of other clustered miRNAs.
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