Related Experiment Video

Updated: Aug 30, 2025

Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins
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Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins

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RBM45 is an m6A-binding protein that affects neuronal differentiation and the splicing of a subset of mRNAs

Seung H Choi1, Mathieu N Flamand1, Bei Liu1

  • 1Department of Biochemistry, Duke University School of Medicine, Durham NC 27710, USA.

Cell Reports
|August 31, 2022
PubMed

Insights

RNA binding protein RBM45 recognizes methylated RNA (m6A) to control mRNA processing and neurodevelopment. RBM45 is crucial for neuronal differentiation and gene expression in the brain.

Area of Science:

  • Molecular Biology
  • Neuroscience
  • Epigenetics

Background:

  • N6-methyladenosine (m6A) is a prevalent RNA modification critical for brain development.
  • The precise mechanisms linking m6A to neurodevelopmental processes remain largely unknown.
  • RBM45, an m6A-binding protein, is highly expressed during neurodevelopment.

Purpose of the Study:

  • To investigate the role of RBM45 in mRNA processing and neurodevelopment.
  • To elucidate how RBM45 recognizes and binds to methylated RNA.
  • To determine the impact of RBM45 depletion on neuronal differentiation and gene expression.

Main Methods:

  • RNA immunoprecipitation (RIP) to identify RBM45-bound RNAs.
  • Analysis of RNA splicing patterns upon RBM45 depletion.
  • Assessment of mRNA and protein level changes.
  • Investigation of neuroblastoma cell differentiation and gene expression pathways.

Main Results:

  • RBM45 binds to thousands of cellular RNAs, primarily in intronic regions.
  • RBM45 depletion perturbs constitutive splicing of specific pre-mRNAs via m6A-dependent and independent pathways.
  • RBM45 is essential for neuroblastoma cell differentiation.
  • RBM45 depletion affects genes involved in neurodevelopmental signaling.

Conclusions:

  • RBM45 plays a significant role in regulating mRNA processing and neuronal differentiation.
  • RBM45's function in the brain is partly mediated by its recognition of methylated RNA.
  • These findings highlight a novel mechanism connecting RNA methylation to neurodevelopmental control.
Keywords:
CP: Developmental biologyCP: Molecular biologyN(6)-methyladenosineRBM45RNA splicingepitranscriptomicsm(6)Aneurobiologyneurodevelopment

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