A conserved nutrient responsive axis mediates autophagic degradation of miRNA-mRNA hybrids in blood cell progenitors

Related Experiment Video

Updated: Jul 10, 2025

Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation
11:06

Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation

Published on: September 20, 2017

6.2K

Sushmit Ghosh1,2, Sreemoyee Chakraborti1,2, Devki Devi1,2

  • 1Developmental Genetic Laboratory, 140306 Punjab, India.

Nucleic Acids Research
|November 23, 2023
PubMed

Insights

Researchers discovered a new pathway where autophagy degrades microRNA-bound messenger RNAs (mRNAs) in response to amino acid deprivation. This process, observed in fruit flies and humans, involves p62 and offers a novel mechanism for cellular waste clearance.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNAs (miRNAs) are key regulators of gene expression in animals, primarily by targeting messenger RNAs (mRNAs).
  • While mRNA and miRNA degradation pathways are known, the role of autophagy in clearing miRNA-target mRNA complexes remains uncharacterized.
  • Understanding these clearance mechanisms is crucial for comprehending cellular homeostasis and gene regulation.

Purpose of the Study:

  • To investigate the involvement of autophagy in the degradation of miRNA and its bound mRNA.
  • To identify novel pathways regulating miRNA and mRNA turnover within the cell.
  • To elucidate the molecular mechanisms underlying the selective clearance of miRNA-target mRNA complexes.

Main Methods:

  • Utilized Drosophila melanogaster and Homo sapiens blood cell progenitors.
  • Investigated the role of amino acid deprivation in triggering cellular degradation pathways.
  • Examined the p62-dependent trafficking of miRNA-mRNA-loaded Argonaute complexes for autophagic degradation.

Main Results:

  • Discovered a leucine-responsive axis mediating autophagy-directed degradation of miRNA-bound mRNA.
  • Demonstrated that amino acid deprivation activates this novel miRNA clearance axis.
  • Showcased a p62-dependent mechanism for trafficking miRNA-mRNA-loaded Argonaute complexes to autophagosomes.
  • Identified a slicer-independent pathway for selective mRNA clearance mediated by autophagy.

Conclusions:

  • Reported a novel autophagy-mediated pathway for the turnover of catalytically active miRNA-induced silencing complexes (miRISCs).
  • Elucidated a slicer-independent mechanism by which autophagy selectively clears target mRNAs bound by miRNAs.
  • This finding provides new insights into post-transcriptional gene regulation and cellular quality control.

More Related Videos

In Vivo Nanovector Delivery of a Heart-specific MicroRNA-sponge09:53

In Vivo Nanovector Delivery of a Heart-specific MicroRNA-sponge

Published on: June 15, 2018

7.4K
Biotin-based Pulldown Assay to Validate mRNA Targets of Cellular miRNAs11:00

Biotin-based Pulldown Assay to Validate mRNA Targets of Cellular miRNAs

Published on: June 12, 2018

13.9K

Related Concept Videos

MicroRNAs01:22

MicroRNAs

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...
3.0K
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
4.3K
Nuclear Export of mRNA02:31

Nuclear Export of mRNA

Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
7.7K
Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

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.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
10.6K
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
3.4K
Regulation of Hematopoietic Stem Cells01:01

Regulation of Hematopoietic Stem Cells

All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
3.2K