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M¹A RNA Modification in Gene Expression Regulation.

ABSTRACT: N¹-methyladenosine (m¹A) is a prevalent and reversible post-transcriptional RNA modification that decorates tRNA, rRNA and mRNA. Recent studies based on technical advances in analytical chemistry and high-throughput sequencing methods have revealed the crucial roles of m¹A RNA modification in gene regulation and biological processes. In this review, we focus on progress in the study of m¹A methyltransferases, m¹A demethylases and m¹A-dependent RNA-binding proteins and highlight the biological mechanisms and functions of m¹A RNA modification, as well as its association with human disease. We also summarize the current understanding of detection approaches for m¹A RNA modification.

SUBMITTER: Jin H

PROVIDER: S-EPMC9141559 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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m1A RNA Modification in Gene Expression Regulation.

Jin Hao H Huo Chunxiao C Zhou Tianhua T Xie Shanshan S

Genes 20220519 5

N1-methyladenosine (m1A) is a prevalent and reversible post-transcriptional RNA modification that decorates tRNA, rRNA and mRNA. Recent studies based on technical advances in analytical chemistry and high-throughput sequencing methods have revealed the crucial roles of m1A RNA modification in gene regulation and biological processes. In this review, we focus on progress in the study of m1A methyltransferases, m1A demethylases and m<su ...[more]

PMID: 35627295

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Project description:ObjectiveSickle cell anemia is a genetic blood disease resulting from production of mutant beta-globin (beta(S)) and has severe clinical consequences. It is known that a higher cellular gamma-globin level, e.g., higher ratio of cellular gamma-globin to beta(S)-globin (gamma/beta(S) ratio), inhibits sickle hemoglobin (HbS) polymerization tendency. Hence, therapeutic treatment of sickle cell anemia has been focused on introducing gamma-globin gene into red blood cells to increase the cellular gamma/beta(S) ratio. Here, we have introduced ribozymes and small interfering RNAs (siRNAs) against beta(S)-globin mRNA into blood cells as a means to increase the gamma/beta(S) ratio.Materials and methodsSingle and multiribozymes against beta(S)-globin mRNA have been tested in vitro and in human erythroleukemia K562beta(S) cells that stably express exogenous beta(S)-globin gene. Primary human hematopoietic progenitor cells were also transfected with multiribozyme and the gamma/(gamma + beta) ratio determined and compared with cells transfected with long hairpin beta-globin cDNA and synthetic siRNA genes.ResultsWe have found that the multiribozyme zb21A containing two ribozyme units effectively reduces beta(S)-globin mRNA both in vitro and in K562beta(S) cells. The gamma-globin mRNA to beta(S)-globin mRNA ratio in the multiribozyme transfected cells is about a factor of 2 more than that in the control cells. We have also found that the gamma/(gamma + beta) ratio in the transfected hematopoietic progenitor cells is increased by more than twofold in cells treated with multiribozyme zb21A or siRNA ib5.ConclusionOur results suggest that introducing multiribozymes or siRNAs into red blood cells is comparable in their effectiveness to increase the ratio of cellular gamma-globin mRNA to beta- or beta(S)-globin mRNA, providing possible strategies to increase the effectiveness of gamma-globin gene transfer as gene therapy for treatment of patients with sickle cell anemia.

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M¹A RNA Modification in Gene Expression Regulation.

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m<sup>1</sup>A RNA Modification in Gene Expression Regulation.

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Dataset Information

M1A RNA Modification in Gene Expression Regulation.

Publications

m<sup>1</sup>A RNA Modification in Gene Expression Regulation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

M¹A RNA Modification in Gene Expression Regulation.