The muscleblind-like (Mbnl) family of RNA-binding proteins plays important roles in muscle and eye development and in myotonic dystrophy (DM), in which expanded CUG or CCUG repeats functionally deplete Mbnl proteins. We identified transcriptome-wide functional and biophysical targets of Mbnl proteins in brain, heart, muscle, and myoblasts by using RNA-seq and CLIP-seq approaches. This analysis identified several hundred splicing events whose regulation depended on Mbnl function in a pattern indicating functional interchangeability between Mbnl1 and Mbnl2. A nucleotide resolution RNA map associated repression or activation of exon splicing with Mbnl binding near either 3' splice site or near the downstream 5' splice site, respectively. Transcriptomic analysis of subcellular compartments uncovered a global role for Mbnls in regulating localization of mRNAs in both mouse and Drosophila cells, and Mbnl-dependent translation and protein secretion were observed for a subset of mRNAs with Mbnl-dependent localization. These findings hold several new implications for DM pathogenesis.

Wang, E., Cody, N., Jog, S., Biancolella, M., Wang, T., Treacy, D., et al. (2012). Transcriptome-wide regulation of pre-mRNA splicing and mRNA localization by muscleblind proteins. CELL, 150(4), 710-724 [10.1016/j.cell.2012.06.041].

Transcriptome-wide regulation of pre-mRNA splicing and mRNA localization by muscleblind proteins

BIANCOLELLA, MICHELA;
2012-01-01

Abstract

The muscleblind-like (Mbnl) family of RNA-binding proteins plays important roles in muscle and eye development and in myotonic dystrophy (DM), in which expanded CUG or CCUG repeats functionally deplete Mbnl proteins. We identified transcriptome-wide functional and biophysical targets of Mbnl proteins in brain, heart, muscle, and myoblasts by using RNA-seq and CLIP-seq approaches. This analysis identified several hundred splicing events whose regulation depended on Mbnl function in a pattern indicating functional interchangeability between Mbnl1 and Mbnl2. A nucleotide resolution RNA map associated repression or activation of exon splicing with Mbnl binding near either 3' splice site or near the downstream 5' splice site, respectively. Transcriptomic analysis of subcellular compartments uncovered a global role for Mbnls in regulating localization of mRNAs in both mouse and Drosophila cells, and Mbnl-dependent translation and protein secretion were observed for a subset of mRNAs with Mbnl-dependent localization. These findings hold several new implications for DM pathogenesis.
2012
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/03 - GENETICA MEDICA
English
3' Untranslated Regions; Animals; DNA-Binding Proteins; Drosophila Proteins; Drosophila melanogaster; Exons; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Myoblasts; Myotonic Dystrophy; Nuclear Proteins; Organ Specificity; RNA Splice Sites; RNA, Messenger; RNA-Binding Proteins; RNA Splicing; Transcriptome
Wang, E., Cody, N., Jog, S., Biancolella, M., Wang, T., Treacy, D., et al. (2012). Transcriptome-wide regulation of pre-mRNA splicing and mRNA localization by muscleblind proteins. CELL, 150(4), 710-724 [10.1016/j.cell.2012.06.041].
Wang, E; Cody, N; Jog, S; Biancolella, M; Wang, T; Treacy, D; Luo, S; Schroth, G; Housman, D; Reddy, S; Lecuyer, E; Burge, C
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/135527
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