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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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Experimental RNAi02:15

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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...
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RNA Interference01:23

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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.
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Regulation of Expression at Multiple Steps01:23

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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...
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To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
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Transcriptional Regulation: Riboswitches01:23

Transcriptional Regulation: Riboswitches

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Riboswitches are RNA elements that regulate gene expression by altering their secondary structures in response to specific effector molecules. These elements, located in the leader regions of certain mRNAs, act as transcriptional regulators by toggling between alternative conformations to control downstream gene expression. Riboswitch-mediated regulation is a precise mechanism for modulating biosynthetic pathways, as exemplified by the riboflavin biosynthesis pathway in Bacillus...
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MicroRNA-based Regulation of Picornavirus Tropism
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MicroRNA function can be reversed by altering target gene expression levels.

Alexander A Svoronos1,2, Stuart G Campbell1, Donald M Engelman2

  • 1Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.

Iscience
|November 10, 2021
PubMed
Summary
This summary is machine-generated.

MicroRNA (miRNA) function, like that of miR-125b, depends on target gene expression. Modifying target levels can reverse miRNA roles in apoptosis, impacting cancer drug efficacy.

Keywords:
Cell biologyComputational bioinformaticsMolecular biologyMolecular mechanism of gene regulation

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression.
  • The function of specific miRNAs, such as miR-125b, can appear contradictory across different biological contexts.
  • miR-125b has been reported to have both pro-apoptotic and anti-apoptotic roles.

Purpose of the Study:

  • To investigate the context-dependent functions of miR-125b in apoptosis.
  • To determine how target gene expression levels influence miR-125b's apoptotic role.
  • To explore the impact of anticancer drugs on miR-125b function.

Main Methods:

  • Utilized a combination of computational modeling and experimental approaches.
  • Analyzed the relationship between miR-125b expression and its pro-apoptotic and anti-apoptotic targets.
  • Investigated the effects of altering target gene expression on miR-125b's function.
  • Assessed the influence of anticancer drugs on miR-125b activity.

Main Results:

  • miR-125b exhibits a pro-apoptotic function when anti-apoptotic targets are overexpressed.
  • miR-125b demonstrates an anti-apoptotic function when pro-apoptotic targets are overexpressed.
  • The function of miR-125b in apoptosis can be completely reversed by manipulating target gene expression levels.
  • Anticancer drugs can alter the functional role of miR-125b.

Conclusions:

  • The function of a microRNA is not fixed and is highly dependent on the expression levels of its target genes.
  • Understanding target gene interactions is crucial for predicting and controlling miRNA function.
  • These findings have implications for miRNA-based therapeutics and understanding drug resistance.