Exogenous leucyl-tRNA synthetase inhibits mouse skeletal muscle differentiation

Zhang, Dayu

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https://hdl.handle.net/2142/115715 Copy

Description

Title

Exogenous leucyl-tRNA synthetase inhibits mouse skeletal muscle differentiation

Author(s)

Zhang, Dayu

Issue Date

2022-04-22

Director of Research (if dissertation) or Advisor (if thesis)

Martinis, Susan A

Doctoral Committee Chair(s)

Martinis, Susan A

Committee Member(s)

• Chen, Jie
• Fratti, Rutilio A
• Kalsotra, Auinash

Department of Study

Biochemistry

Discipline

Biochemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Aminoacyl-tRNA synthetase
• differentiation
• myogenesis
• endocytosis
• C2C12

Abstract

Aminoacyl-tRNA synthetases (AARS) are indispensable for all living organisms. They charge amino acids onto cognate tRNAs. They not only provide critical substrates for ribosomal translation, but are also responsible for correctly delivering messages from mRNA to protein based on the genetic code. In addition to their fundamental translation functions, evolution has taken advantage of AARS binding capacities to ATP, amino acids and tRNAs for alternative, and yet critical regulatory functions. Among them, leucyl-tRNA synthetase (LeuRS) can sense cellular leucine levels to regulate the target of rapamycin complex (TORC) to regulate protein translation, cell proliferation and differentiation. Herein, I showed that exogenous LeuRS can inhibit mouse myoblast C2C12 differentiation. The C2C12 cells show decreased myotube formation and down-regulation of myogenic factor expression. Immunofluorescence staining and confocal microscopy show that exogenous LeuRS can bind to the surface of C2C12 cells, and are internalized in as short as one hour. It is known that C-terminus of LeuRS is involved for various interactions, like RagD, Vps34, and multi-synthetase complex. However, by incubating fragments of LeuRS with C2C12 cells, it turns out that the N-terminus of LeuRS is critical to inhibition of the differentiation process, as well as the binding-internalization process. Collectively, exogenous LeuRS inhibits mouse skeletal muscle cell differentiation. It is consistent with the observation that knocking down endogenous LeuRS stimulates muscle cell differentiation. These parallel studies suggest that intercellular signaling mechanisms for muscle cell differentiation may involve the secretion of LeuRS.

Graduation Semester

2022-05

Type of Resource

Thesis

Copyright and License Information

Copyright 2022 Dayu Zhang

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