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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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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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Nonsense-mediated mRNA Decay02:27

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The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
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The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
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Biotin-based Pulldown Assay to Validate mRNA Targets of Cellular miRNAs
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Linking miRNAs to decay.

Amy E Pasquinelli1

  • 1Molecular Biology Department, School of Biological Sciences, University of California, San Diego, La Jolla, California 92093, USA apasquinelli@ucsd.edu.

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|March 26, 2026
PubMed
Summary
This summary is machine-generated.

A novel long noncoding RNA (lncRNA) mechanism triggers the decay of related microRNAs (miRNAs) through limited base-pairing. This process, target-mediated miRNA decay (TDMD), occurs even with less stringent miRNA-target interactions.

Keywords:
AgoArgonauteEBAX-1RISCZSWIM8miRISCmir-35 family

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Area of Science:

  • Molecular Biology
  • RNA Biology
  • Gene Regulation

Background:

  • MicroRNAs (miRNAs) are key regulators of gene expression, typically functioning within the microRNA (miRNA)-induced silencing complex (miRISC) involving Argonaute (AGO) proteins.
  • miRNA activity is primarily controlled by base-pairing interactions with target messenger RNAs (mRNAs).
  • Target-mediated miRNA decay (TDMD) is a known pathway for miRNA downregulation, but the precise mechanisms and requirements for lncRNA involvement are not fully understood.

Purpose of the Study:

  • To elucidate the mechanism by which a specific long noncoding RNA (lncRNA) coordinately downregulates a family of related microRNAs (miRNAs).
  • To investigate the role of base-pairing complementarity between the lncRNA and miRNAs in triggering miRNA degradation.
  • To determine if TDMD can be induced by lncRNA interactions with less extensive base-pairing than typically observed.

Main Methods:

  • Analysis of miRNA expression profiles in response to lncRNA perturbation.
  • Biochemical assays to assess miRNA-lncRNA binding affinity and stability.
  • RNA immunoprecipitation (RIP) assays to detect miRNA-lncRNA complexes.
  • Reporter assays to quantify miRNA activity and degradation rates.

Main Results:

  • A specific lncRNA was identified that directly interacts with and downregulates a family of related miRNAs.
  • The lncRNA induces target-mediated miRNA decay (TDMD) despite exhibiting limited base-pairing interactions with the target miRNAs.
  • The observed miRNA-lncRNA interactions are sufficient to trigger efficient miRNA degradation, challenging conventional models of TDMD initiation.
  • The study demonstrates coordinate regulation of multiple miRNAs by a single lncRNA through this mechanism.

Conclusions:

  • Long noncoding RNAs can act as potent regulators of miRNA stability and function through TDMD.
  • The findings reveal a novel mechanism for miRNA downregulation mediated by lncRNAs with non-canonical, limited base-pairing interactions.
  • This study expands our understanding of post-transcriptional gene regulation and the diverse roles of lncRNAs in cellular processes.