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m6A Modified Short RNA Fragments Inhibit Cytoplasmic TLS/FUS Aggregation Induced by Hyperosmotic Stress

Ryoma Yoneda1, Naomi Ueda1, Riki Kurokawa1

  • 1Division of Biomedical Sciences, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan.

International Journal of Molecular Sciences
|October 23, 2021
PubMed

Insights

Translocated in Liposarcoma/Fused in Sarcoma (TLS/FUS) binds to m6A modified RNA, influencing its cellular localization and stress resistance. This suggests TLS/FUS is an m6A reader, with m6A RNA enhancing cell survival.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Translocated in Liposarcoma/Fused in Sarcoma (TLS/FUS) is an RNA-binding protein implicated in amyotrophic lateral sclerosis.
  • TLS/FUS participates in liquid-liquid phase separation (LLPS) and forms membraneless organelles.
  • The impact of m6A RNA modification on TLS/FUS-RNA interactions is not well understood.

Purpose of the Study:

  • To investigate the binding specificity of TLS/FUS to m6A-modified RNAs.
  • To determine the functional consequences of m6A RNA interaction with TLS/FUS under stress conditions.

Main Methods:

  • RNA pull-down assays were used to assess TLS/FUS binding to m6A RNA fragments.
  • Cellular localization of TLS/FUS and stress resistance were evaluated after transfection with m6A-modified RNAs.

Main Results:

  • Both wild-type and ALS-mutant TLS/FUS proteins exhibit strong binding to m6A-modified RNAs.
  • m6A-modified RNA transfection reduced TLS/FUS cytoplasmic foci formation under hyperosmotic stress.
  • Cells transfected with m6A-modified RNAs showed increased resistance to hyperosmotic stress.

Conclusions:

  • TLS/FUS is identified as a novel m6A RNA recognition protein.
  • m6A-modified RNAs can diffuse TLS/FUS cytoplasmic foci, enhancing cellular viability under stress.
Keywords:
LLPSRNA m6A modificationTLS/FUSlncRNApncRNA-D

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