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BCDIN3D regulates tRNAHis 3' fragment processing.

Calder W Reinsborough1, Hélène Ipas1, Nathan S Abell1,2

  • 1Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin TX, United States of America.

Plos Genetics
|July 23, 2019
PubMed
Summary
This summary is machine-generated.

BCDIN3D, an RNA methyltransferase, regulates tRNAHis 3'-fragment processing. This enzyme interacts with tRNAHis and a novel microRNA, miR-4454, derived from tRNAHis, without impacting tRNAHis aminoacylation.

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Area of Science:

  • Molecular Biology
  • RNA Biology
  • Biochemistry

Background:

  • The 5' end of RNA molecules dictates their cellular fate.
  • BCDIN3D is an RNA phospho-methyltransferase that modifies the 5' monophosphate of specific RNAs.
  • Understanding BCDIN3D's molecular function requires identifying its interacting RNA partners.

Purpose of the Study:

  • To identify RNAs interacting with BCDIN3D using an unbiased approach.
  • To investigate the biogenesis and regulation of a novel microRNA (miRNA).
  • To elucidate BCDIN3D's role in tRNAHis processing and function.

Main Methods:

  • Thermostable Group II Intron Reverse Transcriptase coupled to next generation sequencing (TGIRT-seq) for RNA interaction analysis.
  • Bioinformatic analysis of RNA sequences and genomic loci.
  • In vitro Dicer cleavage assays using tRNAHis substrates.
  • siRNA-mediated depletion of BCDIN3D in cellular models.

Main Results:

  • BCDIN3D interacts with full-length phospho-methylated tRNAHis and miR-4454.
  • miR-4454 originates from Dicer cleavage of mature tRNAHis, not its annotated locus.
  • BCDIN3D depletion increases tRNAHis 3 '-fragment/miR-4454 levels, indicating BCDIN3D negatively regulates this processing.
  • BCDIN3D does not impair tRNAHis's canonical aminoacylation function.

Conclusions:

  • BCDIN3D regulates the processing of tRNAHis 3 '-fragments, identified as miR-4454.
  • This regulation occurs independently of BCDIN3D's impact on tRNAHis aminoacylation.
  • The study reveals a novel pathway for miRNA biogenesis from tRNA and highlights BCDIN3D's multifaceted role in RNA metabolism.