ROLE OF AKIRIN1 IN STRIATED MUSCLE

Abstract

AKIRIN1 IS A SMALL (191 AMINO ACID) UBIQUITOUSLY EXPRESSED NUCLEAR PROTEIN. PREVIOUS STUDIES HAVE SHOWN THAT AKIRIN1 IS A DOWNSTREAM TARGET OF MYOSTATIN AND CONSISTENT OVER-EXPRESSION OF AKIRIN1 INDUCED HYPERTROPHY IN C2C12 MYOTUBES. USING LOSS OF FUNCTION AKIRIN1 MICE, WE SHOW THAT AKIRIN1 PLAYS AN IMPORTANT ROLE IN REGULATION OF GENES INVOLVED IN MAINTENANCE OF SARCOMERE STRUCTURE AND FUNCTION. ADDITIONALLY, LOSS OF AKIRIN1 AFFECTS THE FIBER TYPE COMPOSITION AND THUS METABOLISM IN FAST TWITCH SKELETAL MUSCLE. HISTOLOGICAL ANALYSIS OF AKIRIN1 KNOCK-OUT HEART SHOWED LARGER VENTRICULAR CAVITY AS SEEN DURING LEFT VENTRICULAR HYPERTROPHY CONDITION. OUR RESULTS SHOW THAT AKIRIN1 IN CARDIAC MUSCLE REGULATES SRF GENE, WHICH IN TURN MAINTAINS CARDIAC MASS THROUGH REGULATING MIR-1 BIOGENESIS. IN SUMMARY, AKIRIN1 HAS A ROLE IN BOTH SKELETAL MUSCLE AND CARDIAC MUSCLE ALBEIT THROUGH DIFFERENT MECHANISMS.