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RNA Catalyst as a Reporter for Screening Drugs against RNA Editing in Trypanosomes
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RNA binding and core complexes constitute the U-insertion/deletion editosome.

Inna Aphasizheva1, Liye Zhang2, Xiaorong Wang3

  • 1Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, Boston, Massachusetts, USA.

Molecular and Cellular Biology
|September 17, 2014
PubMed
Summary
This summary is machine-generated.

Researchers identified the RNA editing substrate binding complex (RESC), a key component of the trypanosomal RNA editing holoenzyme (editosome). RESC binds guide RNAs and pre-mRNAs, linking editing, polyadenylation, and translation.

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Area of Science:

  • Mitochondrial RNA biology
  • Molecular parasitology
  • Gene expression regulation

Background:

  • Trypanosomal mitochondrial mRNAs require U-insertion/deletion editing for functional open reading frames.
  • Guide RNAs (gRNAs) direct the sequential enzymatic reactions of mRNA editing.
  • The RNA editing core complex (RECC) houses the catalytic enzymes for this process.

Purpose of the Study:

  • To define the protein particle responsible for substrate recognition in trypanosomal RNA editing.
  • To elucidate the function of the RNA editing substrate binding complex (RESC).
  • To understand the interplay between RNA editing, polyadenylation, and translation.

Main Methods:

  • Proteomic analysis to identify protein complexes.
  • Genetic manipulation to assess functional roles.
  • RNA sequencing of total and complex-bound RNAs.
  • Biochemical assays to characterize substrate interactions.

Main Results:

  • A 23-polypeptide tripartite assembly, RESC, was identified as the substrate binding component.
  • RESC interfaces with mRNA editing, polyadenylation, and translation machinery.
  • gRNAs, enriched in RESC, possess 3' U-tails and are degraded post-editing.
  • Edited mRNAs are adenylated/uridylated before translation.

Conclusions:

  • The editosome is a ∼40S holoenzyme comprising enzymatic (RECC) and substrate-binding (RESC) constituents.
  • RESC plays a central role in coordinating multiple post-transcriptional processes in the mitochondrion.
  • Distinct metabolic fates of gRNAs and mRNAs highlight regulatory mechanisms within the editosome.