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Diversity in transcriptional start site selection and alternative splicing affects the 5′-UTR of mouse striated muscle myosin transcripts

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Summary

We have analyzed nearly 2,000 myosin heavy chain gene (Myh) clones representing over 30 different transcripts from seven of eight striated muscle Myh genes expressed in mouse. We also report the transcriptional start sites (TSS) for the mouse developmental Myh genes. The data reveal a previously unknown diversity of TSSs and 5′-end alternative splicing in these transcripts. The cardiac Myh6 gene had two major TSSs. Use of the major downstream site led to an alternatively spliced second exon. Each of the other Myh genes had one major TATA-directed TSS and one or more minor alternative TSSs, some associated with alternative splicing. The minor transcripts were associated with polysomes and their spatial-temporal expression largely mirrored that of the major transcripts in wild-type, Myh1 null, Myh4 null, injured, and uninjured muscle, except that one form of Myh7, detected in heart, was not detected in diaphragm, and the ratio of the two major Myh6 transcripts varied in some circumstances. These findings indicate that alternative TSS usage and alternative splicing in the 5′-UTR are a general feature of murine Myh gene expression and that Myh gene regulation is more complex than previously appreciated.

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Acknowledgments

This work was supported by Public Health Service grants NIH GM029090, NIH HL050560, and NIH AR048817 to L. A. L., and NIH 5 P60 DA011015, and NIH 5 R01 DA012845 to K. S. K. Training grant support to B. K. D. was from NIH HL007851. We thank Angelika Paul for cardiotoxin-damaged muscle RNA and mouse anatomy lessons. We thank Matthew Bell for 15.5 and 17.5 dpc mice; Allison Cleary and Doris Beylkin for neonates; Stephen Luckey, Brian Stauffer, Angelika Paul and John Konhilas for general assistance; and Dave Allen for tissue culture lessons. Joseph Heimiller helped with sequence analysis, Eric Robbins helped with DNA preparation and Lindsay Smith helped with PCR.

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  1. Department of Molecular, Cellular and Developmental Biology, University of Colorado at Boulder, Campus Box 347, Boulder, CO, 80309, USA

    Briana K. Dennehey, Leslie A. Leinwand & Kenneth S. Krauter

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  1. Briana K. Dennehey
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Correspondence to Kenneth S. Krauter.

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Dennehey, B.K., Leinwand, L.A. & Krauter, K.S. Diversity in transcriptional start site selection and alternative splicing affects the 5′-UTR of mouse striated muscle myosin transcripts. J Muscle Res Cell Motil 27, 559–575 (2006). https://doi.org/10.1007/s10974-006-9071-8

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