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- W2560652321 abstract "Background. Long noncoding RNAs (lncRNAs) form an abundant class of transcripts that is acquiring an increasing importance due to the roles that some of these molecules have been demonstrated to exert in various biological processes. Unfortunately, the function of the majority of them remains elusive. LncRNA are involved in different epigenetic mechanisms of gene regulation, from chromatin remodelling to post-transcriptional regulation. Since their function is related to their subcellular localization and expression, a genome-wide approach to determine the localization of lncRNAs could greatly improve our understanding of their role in pathophysiology of skeletal muscle.Results. To investigate the subcellular localization of lncRNAs expressed in single skeletal muscle fibers, we studied their compartmentalization by coupling microarray technique with differential extraction and analysis of nuclear and cytoplasmic RNA. We found that 481 lncRNAs preferentially localize in the nucleus, 655 in the cytoplasm and 297 show an alternate localization depending on muscle type and/or lncRNA isoform. Microarray based lncRNA subcellular localization was validated by Fluorescent In Situ Hybridization (FISH) on 6 lncRNAs. All FISH tests confirmed the subcellular localization previously evidenced by the microarray approach. We then chose 32 lncRNAs to investigate their expression profile among different tissues. Of this group, 24 appear to be preferentially expressed in skeletal muscle, 5 in the heart, and only 2 have a high expression in the liver. Skeletal muscle can be approximately classified according contractile capacity as fast and slow, reflecting fiber composition and metabolism. For this reason, we tested the group of 32 lncRNAs for expression in fast or slow myofibers using single-cell analysis, evidencing that 9 lncRNAs have a specific fiber expression probably affecting metabolic traits. To identify lncRNAs involved in skeletal muscle atrophy we also investigated their expression in skeletal muscle during denervation and starvation as well as in a mouse model for Amyotrophic Lateral Sclerosis. We then analysed the expression of the same lncRNAs in proliferating and differentiating C2C12 myoblasts both in purified myonuclei and cytoplasm. 20 lncRNAs presented with differential expression during myogenic differentiation.Conclusions. We localized several lncRNAs inside the skeletal muscle evidencing their preferential expression in this tissue and also in specific myofibers. Moreover, we evidenced that many lncRNAs expressed in the muscle are involved in skeletal muscle atrophy induced by different models and in its differentiation. Finally, we evidenced that lncRNA Pvt1 is able to shuttle between cytoplasm and nucleus during myoblast differentiation in-vitro." @default.
- W2560652321 created "2016-12-16" @default.
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- W2560652321 date "2016-02-01" @default.
- W2560652321 modified "2023-09-24" @default.
- W2560652321 title "The role of long non-coding RNAs in pathophysiological conditions of skeletal muscle" @default.
- W2560652321 hasPublicationYear "2016" @default.
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