Abstract

Muscle-enriched lamin-interacting protein (Mlip) is an alternatively spliced gene whose splicing specificity is dictated by tissue type. MLIP is most abundantly expressed in brain, cardiac, and skeletal muscle. In the present study, we systematically mapped the transcriptional start and stop sites of murine Mlip Rapid amplification of cDNA ends (RACE) of Mlip transcripts from the brain, heart, and skeletal muscle revealed two transcriptional start sites (TSSs), exon 1a and exon 1b, and only one transcriptional termination site. RT-PCR analysis of the usage of the two identified TSSs revealed that the heart utilizes only exon 1a for MLIP expression, whereas the brain exclusively uses exon 1b TSS. Loss of Mlip exon 1a in mice resulted in a 7-fold increase in the prevalence of centralized nuclei in muscle fibers with the Mlip exon1a-deficient satellite cells on single fibers exhibiting a significant delay in commitment to a MYOD-positive phenotype. Furthermore, we demonstrate that the A-type lamin-binding domain in MLIP is encoded in exon 1a, indicating that MLIP isoforms generated with exon 1b TSS lack the A-type lamin-binding domain. Collectively these findings suggest that Mlip tissue-specific expression and alternative splicing play a critical role in determining MLIP's functions in mice.

Highlights

  • Muscle-enriched lamin-interacting protein (Mlip) is an alternatively spliced gene whose splicing specificity is dictated by tissue type

  • Muscle-enriched A-type lamin-interacting protein (Mlip)3 is encoded by a unique gene that is conserved among amniotes

  • The results indicated that the Mlip gene was only expressed in the brain, heart, and hind limb skeletal muscle tissues (Fig. 3B)

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Summary

Introduction

Muscle-enriched lamin-interacting protein (Mlip) is an alternatively spliced gene whose splicing specificity is dictated by tissue type. We demonstrate that the A-type lamin-binding domain in MLIP is encoded in exon 1a, indicating that MLIP isoforms generated with exon 1b TSS lack the A-type lamin-binding domain. These findings suggest that Mlip tissue-specific expression and alternative splicing play a critical role in determining MLIP’s functions in mice. Muscle-enriched A-type lamin-interacting protein (Mlip) is encoded by a unique gene that is conserved among amniotes. The aim of the present study was to investigate and define the expression of the Mlip gene and to characterize the different alternatively spliced forms in individual tissues. We demonstrate that cellular localization and functionality are dictated by alternative expression and splicing of MLIP isoforms

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