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MicroRNAs01:22

MicroRNAs

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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
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MicroRNAs01:22

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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
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Pre-mRNA Processing: Modification of pre-mRNA Ends01:35

Pre-mRNA Processing: Modification of pre-mRNA Ends

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In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a cap to the 5' end of the growing transcript. In this process, a 5' phosphate is replaced by modified guanosine that has a methyl group attached (7-methyl guanosine). This 5' cap helps...
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pre-mRNA Processing02:01

pre-mRNA Processing

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In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a “cap” to the 5’ end of the growing transcript. In this process, a 5’ phosphate is replaced by modified guanosine that has a methyl group attached to it (7-Methyl...
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Related Experiment Video

Updated: Apr 15, 2026

A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues
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A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues

Published on: December 5, 2016

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N6-methyladenosine marks primary microRNAs for processing.

Claudio R Alarcón1, Hyeseung Lee1, Hani Goodarzi1

  • 1Laboratory of Systems Cancer Biology, Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.

Nature
|March 25, 2015
PubMed
Summary
This summary is machine-generated.

Methyltransferase-like 3 (METTL3) adds an m(6)A mark to pri-miRNAs, enabling DGCR8 recognition and microRNA processing. This modification is essential for miRNA biogenesis and global miRNA levels.

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Area of Science:

  • Molecular Biology
  • RNA Biology
  • Epigenetics

Background:

  • MicroRNA (miRNA) biogenesis initiates with primary miRNA (pri-miRNA) processing by the microprocessor complex (DGCR8/DROSHA).
  • The precise mechanism of DGCR8 recognition of pri-miRNAs over other RNA structures remains unclear.

Purpose of the Study:

  • To elucidate the mechanism by which DGCR8 recognizes and binds pri-miRNAs.
  • To identify factors regulating the initial step of miRNA biogenesis.

Main Methods:

  • Cellular experiments involving METTL3 depletion and gain-of-function.
  • Biochemical assays including in vitro processing reactions.
  • Analysis of pri-miRNA and mature miRNA levels.

Main Results:

  • METTL3 methylates pri-miRNAs at the N(6)-methyladenosine (m(6)A) site, marking them for DGCR8 binding.
  • METTL3 depletion reduces DGCR8-pri-miRNA interaction, leading to decreased mature miRNA and increased pri-miRNA levels.
  • In vitro studies confirm m(6)A sufficiency for pri-miRNA processing; METTL3 enhances miRNA maturation globally.

Conclusions:

  • The m(6)A modification, mediated by METTL3, is a critical post-transcriptional regulator that promotes pri-miRNA recognition and processing by DGCR8.
  • This finding reveals a novel mechanism controlling the initiation of miRNA biogenesis.