title: Alternative splicing of a viral mirtron differentially affects the expression of other microRNAs from its cluster and of the host transcript.
abstract: 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.
authors.affiliation: a Equipe Transcription et Lymphome Viro-Induit (TLVI), UMR 7261 CNRS, Université François Rabelais , Parc de Grandmont , Tours , France.
authors.forename: Perrine
authors.initials: P
authors.lastname: Rasschaert
authors.affiliation: a Equipe Transcription et Lymphome Viro-Induit (TLVI), UMR 7261 CNRS, Université François Rabelais , Parc de Grandmont , Tours , France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Figueroa
authors.affiliation: a Equipe Transcription et Lymphome Viro-Induit (TLVI), UMR 7261 CNRS, Université François Rabelais , Parc de Grandmont , Tours , France.
authors.forename: Ginette
authors.initials: G
authors.lastname: Dambrine
authors.affiliation: a Equipe Transcription et Lymphome Viro-Induit (TLVI), UMR 7261 CNRS, Université François Rabelais , Parc de Grandmont , Tours , France.
authors.forename: Denis
authors.initials: D
authors.lastname: Rasschaert
authors.affiliation: a Equipe Transcription et Lymphome Viro-Induit (TLVI), UMR 7261 CNRS, Université François Rabelais , Parc de Grandmont , Tours , France.|b Département de Santé Animale , INRA , Nouzilly , France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Laurent
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002460:Cell Line; D002645:Chickens / Q000821:virology; D015967:Gene Expression Regulation, Viral; D025922:Mardivirus / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D005810:Multigene Family; D062085:RNA, Long Noncoding / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics
chemical_list: D035683:MicroRNAs; D062085:RNA, Long Noncoding; D012367:RNA, Viral
keywords: Cluster of microRNAs; Marek's disease virus; long non-coding RNA; mirtron; splicing