BCDIN3D regulates tRNAHis 3’ fragment processing

Calder W. Reinsborough, Hélène Ipas, Nathan S. Abell, Ryan M. Nottingham, Jun Yao, Sravan K. Devanathan, Samantha B. Shelton, Alan M. Lambowitz, Blerta Xhemalçe

Research output: Contribution to journalArticle

Abstract

5’ ends are important for determining the fate of RNA molecules. BCDIN3D is an RNA phospho-methyltransferase that methylates the 5’ monophosphate of specific RNAs. In order to gain new insights into the molecular function of BCDIN3D, we performed an unbiased analysis of its interacting RNAs by Thermostable Group II Intron Reverse Transcriptase coupled to next generation sequencing (TGIRT-seq). Our analyses showed that BCDIN3D interacts with full-length phospho-methylated tRNAHis and miR-4454. Interestingly, we found that miR-4454 is not synthesized from its annotated genomic locus, which is a primer-binding site for an endogenous retrovirus, but rather by Dicer cleavage of mature tRNAHis. Sequence analysis revealed that miR-4454 is identical to the 3’ end of tRNAHis. Moreover, we were able to generate this ‘miRNA’ in vitro through incubation of mature tRNAHis with Dicer. As found previously for several pre-miRNAs, a 5’P-tRNAHis appears to be a better substrate for Dicer cleavage than a phospho-methylated tRNAHis. Moreover, tRNAHis 3’-fragment/‘miR-4454’ levels increase in cells depleted for BCDIN3D. Altogether, our results show that in addition to microRNAs, BCDIN3D regulates tRNAHis 3’-fragment processing without negatively affecting tRNAHis’s canonical function of aminoacylation.

Original languageEnglish (US)
Article numbere1008273
JournalPLoS Genetics
Volume15
Issue number7
DOIs
StatePublished - Jul 2019

Fingerprint

RNA, Transfer, His
RNA
microRNA
cleavage
Retroviridae
aminoacylation
MicroRNAs
RNA-directed DNA polymerase
methyltransferases
introns
binding sites
genomics
sequence analysis
incubation
Aminoacylation
Endogenous Retroviruses
substrate
loci
RNA-Directed DNA Polymerase
Methyltransferases

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Reinsborough, C. W., Ipas, H., Abell, N. S., Nottingham, R. M., Yao, J., Devanathan, S. K., ... Xhemalçe, B. (2019). BCDIN3D regulates tRNAHis 3’ fragment processing. PLoS Genetics, 15(7), [e1008273]. https://doi.org/10.1371/journal.pgen.1008273

BCDIN3D regulates tRNAHis 3’ fragment processing. / Reinsborough, Calder W.; Ipas, Hélène; Abell, Nathan S.; Nottingham, Ryan M.; Yao, Jun; Devanathan, Sravan K.; Shelton, Samantha B.; Lambowitz, Alan M.; Xhemalçe, Blerta.

In: PLoS Genetics, Vol. 15, No. 7, e1008273, 07.2019.

Research output: Contribution to journalArticle

Reinsborough, CW, Ipas, H, Abell, NS, Nottingham, RM, Yao, J, Devanathan, SK, Shelton, SB, Lambowitz, AM & Xhemalçe, B 2019, 'BCDIN3D regulates tRNAHis 3’ fragment processing', PLoS Genetics, vol. 15, no. 7, e1008273. https://doi.org/10.1371/journal.pgen.1008273
Reinsborough CW, Ipas H, Abell NS, Nottingham RM, Yao J, Devanathan SK et al. BCDIN3D regulates tRNAHis 3’ fragment processing. PLoS Genetics. 2019 Jul;15(7). e1008273. https://doi.org/10.1371/journal.pgen.1008273
Reinsborough, Calder W. ; Ipas, Hélène ; Abell, Nathan S. ; Nottingham, Ryan M. ; Yao, Jun ; Devanathan, Sravan K. ; Shelton, Samantha B. ; Lambowitz, Alan M. ; Xhemalçe, Blerta. / BCDIN3D regulates tRNAHis 3’ fragment processing. In: PLoS Genetics. 2019 ; Vol. 15, No. 7.
@article{14c325830e394e2e892f33475b7ca300,
title = "BCDIN3D regulates tRNAHis 3’ fragment processing",
abstract = "5’ ends are important for determining the fate of RNA molecules. BCDIN3D is an RNA phospho-methyltransferase that methylates the 5’ monophosphate of specific RNAs. In order to gain new insights into the molecular function of BCDIN3D, we performed an unbiased analysis of its interacting RNAs by Thermostable Group II Intron Reverse Transcriptase coupled to next generation sequencing (TGIRT-seq). Our analyses showed that BCDIN3D interacts with full-length phospho-methylated tRNAHis and miR-4454. Interestingly, we found that miR-4454 is not synthesized from its annotated genomic locus, which is a primer-binding site for an endogenous retrovirus, but rather by Dicer cleavage of mature tRNAHis. Sequence analysis revealed that miR-4454 is identical to the 3’ end of tRNAHis. Moreover, we were able to generate this ‘miRNA’ in vitro through incubation of mature tRNAHis with Dicer. As found previously for several pre-miRNAs, a 5’P-tRNAHis appears to be a better substrate for Dicer cleavage than a phospho-methylated tRNAHis. Moreover, tRNAHis 3’-fragment/‘miR-4454’ levels increase in cells depleted for BCDIN3D. Altogether, our results show that in addition to microRNAs, BCDIN3D regulates tRNAHis 3’-fragment processing without negatively affecting tRNAHis’s canonical function of aminoacylation.",
author = "Reinsborough, {Calder W.} and H{\'e}l{\`e}ne Ipas and Abell, {Nathan S.} and Nottingham, {Ryan M.} and Jun Yao and Devanathan, {Sravan K.} and Shelton, {Samantha B.} and Lambowitz, {Alan M.} and Blerta Xhemal{\cc}e",
year = "2019",
month = "7",
doi = "10.1371/journal.pgen.1008273",
language = "English (US)",
volume = "15",
journal = "PLoS Genetics",
issn = "1553-7390",
publisher = "Public Library of Science",
number = "7",

}

TY - JOUR

T1 - BCDIN3D regulates tRNAHis 3’ fragment processing

AU - Reinsborough, Calder W.

AU - Ipas, Hélène

AU - Abell, Nathan S.

AU - Nottingham, Ryan M.

AU - Yao, Jun

AU - Devanathan, Sravan K.

AU - Shelton, Samantha B.

AU - Lambowitz, Alan M.

AU - Xhemalçe, Blerta

PY - 2019/7

Y1 - 2019/7

N2 - 5’ ends are important for determining the fate of RNA molecules. BCDIN3D is an RNA phospho-methyltransferase that methylates the 5’ monophosphate of specific RNAs. In order to gain new insights into the molecular function of BCDIN3D, we performed an unbiased analysis of its interacting RNAs by Thermostable Group II Intron Reverse Transcriptase coupled to next generation sequencing (TGIRT-seq). Our analyses showed that BCDIN3D interacts with full-length phospho-methylated tRNAHis and miR-4454. Interestingly, we found that miR-4454 is not synthesized from its annotated genomic locus, which is a primer-binding site for an endogenous retrovirus, but rather by Dicer cleavage of mature tRNAHis. Sequence analysis revealed that miR-4454 is identical to the 3’ end of tRNAHis. Moreover, we were able to generate this ‘miRNA’ in vitro through incubation of mature tRNAHis with Dicer. As found previously for several pre-miRNAs, a 5’P-tRNAHis appears to be a better substrate for Dicer cleavage than a phospho-methylated tRNAHis. Moreover, tRNAHis 3’-fragment/‘miR-4454’ levels increase in cells depleted for BCDIN3D. Altogether, our results show that in addition to microRNAs, BCDIN3D regulates tRNAHis 3’-fragment processing without negatively affecting tRNAHis’s canonical function of aminoacylation.

AB - 5’ ends are important for determining the fate of RNA molecules. BCDIN3D is an RNA phospho-methyltransferase that methylates the 5’ monophosphate of specific RNAs. In order to gain new insights into the molecular function of BCDIN3D, we performed an unbiased analysis of its interacting RNAs by Thermostable Group II Intron Reverse Transcriptase coupled to next generation sequencing (TGIRT-seq). Our analyses showed that BCDIN3D interacts with full-length phospho-methylated tRNAHis and miR-4454. Interestingly, we found that miR-4454 is not synthesized from its annotated genomic locus, which is a primer-binding site for an endogenous retrovirus, but rather by Dicer cleavage of mature tRNAHis. Sequence analysis revealed that miR-4454 is identical to the 3’ end of tRNAHis. Moreover, we were able to generate this ‘miRNA’ in vitro through incubation of mature tRNAHis with Dicer. As found previously for several pre-miRNAs, a 5’P-tRNAHis appears to be a better substrate for Dicer cleavage than a phospho-methylated tRNAHis. Moreover, tRNAHis 3’-fragment/‘miR-4454’ levels increase in cells depleted for BCDIN3D. Altogether, our results show that in addition to microRNAs, BCDIN3D regulates tRNAHis 3’-fragment processing without negatively affecting tRNAHis’s canonical function of aminoacylation.

UR - http://www.scopus.com/inward/record.url?scp=85071061175&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85071061175&partnerID=8YFLogxK

U2 - 10.1371/journal.pgen.1008273

DO - 10.1371/journal.pgen.1008273

M3 - Article

C2 - 31329584

AN - SCOPUS:85071061175

VL - 15

JO - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7390

IS - 7

M1 - e1008273

ER -