RGD Reference Report - Self-regulated alternative splicing at the AHNAK locus. - Rat Genome Database

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Self-regulated alternative splicing at the AHNAK locus.

Authors: De Morree, A  Droog, M  Grand Moursel, L  Bisschop, IJ  Impagliazzo, A  Frants, RR  Klooster, R  Van der Maarel, SM 
Citation: de Morree A, etal., FASEB J. 2012 Jan;26(1):93-103. doi: 10.1096/fj.11-187971. Epub 2011 Sep 22.
RGD ID: 8554027
Pubmed: PMID:21940993   (View Abstract at PubMed)
DOI: DOI:10.1096/fj.11-187971   (Journal Full-text)

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.

Objects referenced in this article
Gene AC141959.1 null Rattus norvegicus
Gene Ahnak2 AHNAK nucleoprotein 2 Rattus norvegicus

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