Impairing the microRNA biogenesis pathway induces proteome modifications characterized by size bias and enrichment in

Delphine Peric1, Jean Labarre, François Chevalier

  • 1Commissariat à l'Energie Atomique, Laboratoire de Génétique de la Radiosensibilité, Fontenay aux Roses, France.

Proteomics
|August 14, 2012
PubMed

Insights

Inhibition of microRNA biogenesis causes cancer cell growth arrest and alters protein expression, favoring smaller proteins. This size bias in proteome changes also occurs during oxidative stress, suggesting a role for microRNAs in proteostasis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • MicroRNA (miRNA) pathway perturbation is implicated in cancer development.
  • Inhibition of miRNA biogenesis can induce a cell growth arrest state (CoGAM), which is reversible by miRNA re-expression.

Purpose of the Study:

  • To investigate proteome modifications induced by miRNA biogenesis inhibition.
  • To explore the relationship between miRNA pathway, stress responses, and protein size bias.

Main Methods:

  • Mass spectrometry-based proteomics to analyze protein expression changes.
  • Gene Ontology (GO) analysis to identify enriched protein functions.
  • Experimental induction of oxidative stress using H(2)O(2) in yeast and mammalian cells.

Main Results:

  • miRNA biogenesis inhibition leads to a proteome size bias, with increased small proteins and decreased large proteins.
  • This size bias is observed in CoGAM-sensitive, CoGAM-resistant, and rescued cells.
  • Proteins induced during CoGAM are enriched in pathways related to oxidative stress resistance.
  • Oxidative stress independently induces similar size-biased proteome modifications.

Conclusions:

  • Proteome size bias is a significant indicator of cellular stress, including miRNA pathway disruption and oxidative stress.
  • The miRNA pathway may play a crucial role in maintaining proteostasis under stress conditions.
  • Further research into miRNA's role in proteostasis is warranted.

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...
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 ends...
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 ends...
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...
RNA Interference01:23

RNA Interference

RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...