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piRNA - Piwi-interacting RNAs02:57

piRNA - Piwi-interacting RNAs

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PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...
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DNA-only Transposons02:57

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DNA-only transposons are called autonomous transposons since they code for the enzyme transposase that is required for the transposition mechanism. Insertion of transposons can alter gene functions in multiple ways. They can mutate the gene, alter gene expression by introducing a novel promoter or insulator sequence, introduce new splice sites, and change the mRNA transcripts produced, or remodel chromatin structure.
The donor site from where the transposon is excised is either degraded or...
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RNA Interference01:23

RNA Interference

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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.
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...
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siRNA - Small Interfering RNAs02:30

siRNA - Small Interfering RNAs

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Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
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Experimental RNAi02:15

Experimental RNAi

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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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Transposons01:24

Transposons

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Transposons, or "jumping genes," are small mobile genetic elements (MGEs) that range from 700 to 40,000 base pairs in length. They are found in all organisms and can move within the same chromosome or transfer to different chromosomes. In some cases, transposons can also jump between different host DNA molecules, such as plasmids or viruses, contributing to genetic variability.Barbara McClintock first discovered these mobile genetic elements in the 1940s while studying maize genetics, and she...
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Related Experiment Video

Updated: Jul 26, 2025

Real-Time Quantification of the Effects of IS200/IS605 Family-Associated TnpB on Transposon Activity
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Real-Time Quantification of the Effects of IS200/IS605 Family-Associated TnpB on Transposon Activity

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Relaxed targeting rules help PIWI proteins silence transposons.

Ildar Gainetdinov1, Joel Vega-Badillo2, Katharine Cecchini2

  • 1RNA Therapeutics Institute and Howard Hughes Medical Institute, University of Massachusetts Chan Medical School, Worcester, MA, USA. ildar.gainetdinov@umassmed.edu.

Nature
|June 21, 2023
PubMed
Summary

PIWI proteins, unlike AGO proteins, efficiently cleave partially matched transcripts using PIWI-interacting RNAs (piRNAs). This mismatch tolerance allows PIWI proteins to better defend genomes against transposons without needing new small RNA guides.

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Area of Science:

  • Molecular Biology
  • Genetics
  • RNA Biology

Background:

  • Eukaryotes utilize small RNAs (siRNAs, miRNAs) to guide AGO proteins for gene regulation and genome defense.
  • Animal-specific PIWI proteins use PIWI-interacting RNAs (piRNAs) to silence transposon transcripts.
  • Transposons may evade silencing via mutations reducing piRNA complementarity.

Purpose of the Study:

  • To investigate the target binding and cleavage capabilities of PIWI proteins compared to AGO proteins.
  • To determine the tolerance of PIWI proteins to mismatches in piRNA-target interactions.
  • To understand the evolutionary advantage of the PIWI-piRNA pathway in genome defense.

Main Methods:

  • Examination of target binding and cleavage by mouse and sponge PIWI proteins.
  • Analysis of PIWI protein activity with partially paired target transcripts.
  • Comparison of PIWI protein mismatch tolerance with known AGO protein requirements.

Main Results:

  • PIWI proteins efficiently cleave transcripts with partial pairing to piRNA guides.
  • PIWI slicing tolerates mismatches at any target nucleotide, including around the scissile phosphate.
  • Canonical seed pairing is not essential for PIWI binding or cleavage, unlike AGO proteins.

Conclusions:

  • PIWI proteins exhibit superior capability over AGO proteins in targeting evolving transposons.
  • The PIWI pathway's tolerance to mismatches provides robust defense against transposons.
  • This mechanism explains the retention of the PIWI-piRNA pathway in animal evolution for genome defense.