Self-regulated alternative splicing at the AHNAK locus

Autor: Laure Grand Moursel, Silvère M. van der Maarel, Marjolein Droog, Rinse Klooster, Antoine de Morrée, Antonietta Impagliazzo, Ilona J.M. Bisschop, Rune R. Frants
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Gene isoform
Protein isoform
RNA
Messenger/genetics
Dysferlinopathy
Myoblasts
Skeletal
Molecular Sequence Data
muscle differentiation
Calcium Signaling/physiology
Biochemistry
Gene Expression Regulation/genetics
Feedback
Physiological/physiology
Dysferlin
Evolution
Molecular
Exon
Mice
Neoplasm Proteins/genetics
Gene expression
Genetics
medicine
Animals
Cell Differentiation/physiology
Humans
Calcium Signaling
RNA
Messenger
Amino Acid Sequence
RNA Processing
Post-Transcriptional
Membrane Proteins/genetics
Molecular Biology
Cells
Cultured
Phylogeny
Feedback
Physiological
Alternative Splicing/physiology
biology
RNA Processing
Post-Transcriptional/physiology
Alternative splicing
Membrane Proteins
Cell Differentiation
RNA expression
medicine.disease
LGMD
Myoblasts
Skeletal/cytology
Neoplasm Proteins
Cell biology
Alternative Splicing
Gene Expression Regulation
RNA splicing
biology.protein
Biotechnology
Zdroj: de Morrée, A, Droog, M, Grand Moursel, L, Bisschop, I J M, Impagliazzo, A, Frants, R R, Klooster, R & van der Maarel, S M 2012, ' Self-regulated alternative splicing at the AHNAK locus ', FASEB journal : official publication of the Federation of American Societies for Experimental Biology, vol. 26, no. 1, pp. 93-103 . https://doi.org/10.1096/fj.11-187971
FASEB Journal, 26(1), 93-103
DOI: 10.1096/fj.11-187971
Popis: AHNAK is a 700-kDa protein involved in cytoarchitecture and calcium signaling. It is secondarily reduced in muscle of dysferlinopathy patients and accumulates in muscle of calpainopathy patients, both affected by a muscular dystrophy. AHNAK directly interacts with dysferlin. This interaction is lost on cleavage of AHNAK by the protease calpain 3, explaining the molecular observations in patients. Currently, little is known of AHNAK regulation. We describe the self-regulation of multiple mRNA transcripts emanating from the AHNAK locus in muscle cells. We show that the AHNAK gene consists of a 17-kb exon flanked by multiple small exons. This genetic structure is shared by AHNAK2 and Periaxin, which share a common ancestor. Two major AHNAK transcripts are differentially expressed during muscle differentiation that encode for a small (17-kDa) and a large (700-kDa) protein isoform. These proteins interact in the cytoplasm, but the small AHNAK is also present in the nucleus. During muscle differentiation the small AHNAK is strongly increased, thereby establishing a positive feedback loop to regulate mRNA splicing of its own locus. A small 17-kDa isoform of Periaxin similarly traffics between the cytoplasm and the nucleus to regulate mRNA splicing. Thus, AHNAK constitutes a novel mechanism in post-transcriptional control of gene expression.
Databáze: OpenAIRE
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