Cardiovascular Division, BHF Centre of Research Excellence, King's College London, London, UK.
J Muscle Res Cell Motil. 2012 Jun;33(2):107-22. doi: 10.1007/s10974-012-9288-7. Epub 2012 Mar 17.
The striated muscle-specific tripartite motif (TRIM) proteins TRIM63/MURF1, TRIM55/MURF2 and TRIM54/MURF3 can function as E3 ubiquitin ligases in ubiquitin-mediated muscle protein turnover. Despite the well-characterised role of MURF1 in skeletal muscle atrophy, the dynamics of MURF isogene expression in the development and early postnatal adaptation of skeletal muscle is unknown. Here, we show that MURF2 is the isogene most highly expressed in embryonic skeletal muscle at E15.5, with the 50 kDa A isoform predominantly expressed. MURF1 and MURF3 are upregulated only postnatally. Knockdown of MURF2 p50A by isoform-specific siRNA results in delayed myogenic differentiation and myotube formation in vitro, with perturbation of the stable, glutamylated microtubule population. This underscores that MURF2 plays an important role in the earliest stages of skeletal muscle differentiation and myofibrillogenesis. During further development, there is a shift towards the 60 kDa A isoform, which dominates postnatally. Analysis of the fibre-type expression shows that MURF2 A isoforms are predominantly slow-fibre associated, whilst MURF1 is largely excluded from these fibres, and MURF3 is ubiquitously distributed in both type I and II fibres.
横纹肌特异性三联基序（TRIM）蛋白 TRIM63/MURF1、TRIM55/MURF2 和 TRIM54/MURF3 可以作为 E3 泛素连接酶，在泛素介导的肌肉蛋白周转中发挥作用。尽管 MURF1 在骨骼肌萎缩中的作用已得到很好的描述，但 MURF 同工型表达的动力学在骨骼肌的发育和出生后早期适应中尚不清楚。在这里，我们表明 MURF2 是在 E15.5 时胚胎骨骼肌中表达最高的同工型，主要表达 50 kDa A 同工型。MURF1 和 MURF3 仅在出生后上调。通过同工型特异性 siRNA 敲低 MURF2 p50A 会导致体外成肌分化和肌管形成延迟，稳定的、谷氨酸化的微管群受到干扰。这强调了 MURF2 在骨骼肌分化和肌原纤维发生的最早阶段发挥重要作用。在进一步发育过程中，向 60 kDa A 同工型转变，该同工型在出生后占主导地位。对纤维型表达的分析表明，MURF2 A 同工型主要与慢肌相关，而 MURF1 则主要排除在这些纤维之外，MURF3 则均匀分布在 I 型和 II 型纤维中。
