Mismatched and wobble base pairs govern primary microRNA processing by human Microprocessor

Autor: Li, Shaohua, Nguyen, Trung Duc, Nguyen, Thuy Linh, Nguyen, Tuan Anh
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Ribonuclease III
0301 basic medicine
Molecular biology
Science
Gene Expression
General Physics and Astronomy
Single-nucleotide polymorphism
Wobble base pair
Computational biology
Biology
Polymorphism
Single Nucleotide
Biochemistry
Article
General Biochemistry
Genetics and Molecular Biology
law.invention
03 medical and health sciences
0302 clinical medicine
law
Gene expression
microRNA
Humans
RNA Processing
Post-Transcriptional
Author Correction
lcsh:Science
Base Pairing
Gene
Multidisciplinary
Primary MicroRNA
Sequence Analysis
RNA
RNA-Binding Proteins
RNA
General Chemistry
HCT116 Cells
Recombinant Proteins
MicroRNAs
Microprocessor
HEK293 Cells
030104 developmental biology
ComputingMethodologies_PATTERNRECOGNITION
Nucleic Acid Conformation
RNA Interference
lcsh:Q
RNA Editing
030217 neurology & neurosurgery
Zdroj: Nature Communications, Vol 11, Iss 1, Pp 1-17 (2020)
Nature Communications
ISSN: 2041-1723
Popis: MicroRNAs (miRNAs) are small RNAs that regulate gene expression. miRNAs are produced from primary miRNAs (pri-miRNAs), which are cleaved by Microprocessor. Microprocessor, therefore, plays a crucial role in determining the efficiency and precision of miRNA production, and thus the function of the final miRNA product. Here, we conducted high-throughput enzymatic assays to investigate the catalytic mechanism of Microprocessor cleaving randomized pri-miRNAs. We identified multiple mismatches and wobble base pairs in the upper stem of pri-miRNAs, which influence the efficiency and accuracy of their processing. The existence of these RNA elements helps to explain the alternative cleavage of Microprocessor for some human pri-miRNAs. We also demonstrated that miRNA biogenesis can be altered via modification of the RNA elements by RNA-editing events or single nucleotide polymorphisms (SNPs). These findings improve our understanding of pri-miRNA processing mechanisms and provide a foundation for interpreting differential miRNA expression due to RNA modifications and SNPs.
MicroRNA genes are transcribed to long primary transcripts called primary microRNAs, which are cleaved by Microprocessor. Here the authors employ high-throughput sequencing and Microprocessor assay to show that mismatches and wobble base pairs in primary microRNAs affect the accuracy and efficiency of Microprocessor processing.
Databáze: OpenAIRE
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