The mammalian LINC complex component SUN1 regulates muscle regeneration by modulating drosha activity

Here we show that a major muscle specific isoform of the murine LINC complex protein SUN1 is required for efficient muscle regeneration. The nucleoplasmic domain of the isoform specifically binds to and inhibits Drosha, a key component of the microprocessor complex required for miRNA synthesis. Comparison of the miRNA profiles between wildtype and SUN1 null myotubes identified a cluster of miRNAs encoded by a non-translated retrotransposon-like one antisense (Rtl1as) transcript that are decreased in the WT myoblasts due to SUN1 inhibition of Drosha. One of these miRNAs miR-127 inhibits the translation of the Rtl1 sense transcript, that encodes the retrotransposon-like one protein (RTL1), which is also required for muscle regeneration and is expressed in regenerating/dystrophic muscle. The LINC complex may therefore regulate gene expression during muscle regeneration by controlling miRNA processing. This provides new insights into the molecular pathology underlying muscular dystrophies and how the LINC complex may regulate mechanosignaling.

A Pair of Partially Overlapping Arabidopsis Genes with Antagonistic Circadian Expression

A large number of plant genes are aligned with partially overlapping genes in antisense orientation. Transcription of both genes would therefore favour the formation of double-stranded RNA, providing a substrate for the RNAi machinery, and enhanced antisense transcription should therefore reduce sense transcript levels. We have identified a gene pair that resembles a model for antisense-based gene regulation as a T-DNA insertion into the antisense gene causes a reduction in antisense transcript levels and an increase in sense transcript levels. The same effect was, however, also observed when the two genes were inserted as transgenes into different chromosomal locations, independent of the sense and antisense gene being expressed individually or jointly. Our results therefore indicate that antagonistic changes in sense/antisense transcript levels do not necessarily reflect antisense-mediated regulation. More likely, the partial overlap of the two genes may have favoured the evolution of antagonistic expression patterns preventing RNAi effects.