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This Article Full Text Free Full Text (PDF) Free Supplemental Data All Versions of this Article: fj.08-125542v1 23/6/1988    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Li, H. Articles by Du, S.-J. Search for Related Content PubMed PubMed Citation Articles by Li, H. Articles by Du, S.-J.

skNAC (skeletal Naca), a muscle-specific isoform of Naca (nascent polypeptide-associated complex alpha), is required for myofibril organization

Huiqing Li^*, William R. Randall and Shao-Jun Du^*,1

^* Center of Marine Biotechnology, University of Maryland Biotechnology Institute, Baltimore, Maryland, USA; and

Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, Maryland, USA

¹Correspondence: Center of Marine Biotechnology, University of Maryland Biotechnology Institute, 701 E. Pratt St., Baltimore, MD 21202, USA. E-mail: dus{at}umbi.umd.edu

Myofibrillogenesis, the precise assembly of sarcomeric proteins into the highly organized sarcomeres, is essential for muscle cell differentiation and function. Myofibrillogenesis requires proper folding and assembly of newly synthesized sarcomeric proteins. sknac (skeletal naca) is an alternatively spliced isoform of naca, which encodes the nascent polypeptide-associated complex alpha polypeptide that binds to newly synthesized polypeptides emerging from the ribosome. sknac is specifically expressed in skeletal and cardiac muscles. However, little is known about the function of skNAC in muscle development in vivo. To determine skNAC function, we have isolated and characterized the sknac gene from zebrafish. Zebrafish sknac cDNA differs from naca by containing an extra large exon that encodes 815 aa. Knockdown of sknac expression by antisense oligos resulted in zebrafish embryos with skeletal muscle defects. The sknac-knockdown embryos showed a paralyzed phenotype with little muscle contraction. In contrast, injection of a control oligo had no effect. Immunostaining and histological analyses revealed that sknac-knockdown embryos contained disorganized thick and thin filaments. Western blot analysis revealed that myosin protein levels were significantly reduced. Collectively, these results demonstrate that skNAC plays a vital role in myofibril assembly and function during muscle cell differentiation.—Li, H., Randall, W. R., Du, S.-J. skNAC (skeletal Naca), a muscle-specific isoform of Naca (nascent polypeptide-associated complex alpha), is required for myofibril organization in zebrafish embryo.

Key Words: thick filament • myofibrillogenesis • myosin • sarcomere