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Related Concept Videos

RNA Editing02:23

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RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
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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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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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In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
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Updated: Jun 29, 2025

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Improving prime editing with an endogenous small RNA-binding protein.

Jun Yan1, Paul Oyler-Castrillo2, Purnima Ravisankar2,3

  • 1Department of Molecular Biology, Princeton University, Princeton, NJ, USA.

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|April 3, 2024
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Summary

The La protein significantly enhances prime editing, a precise genome editing technology. Researchers developed an improved prime editor (PE7) by fusing it with La, boosting editing efficiency.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biotechnology

Background:

  • Prime editing is a powerful genome editing technology that allows for precise DNA modifications.
  • Understanding cellular factors that influence prime editing efficiency is crucial for its optimization.

Purpose of the Study:

  • To identify cellular determinants that mediate prime editing efficiency.
  • To develop an enhanced prime editing system based on identified factors.

Main Methods:

  • Developed scalable prime editing reporters.
  • Performed genome-scale CRISPR-interference screens to identify host factors.
  • Investigated the interaction of the La protein with prime editing guide RNAs (pegRNAs).
  • Engineered a novel prime editor (PE7) by fusing it with the La protein.

Main Results:

  • The La protein was identified as a key mediator of prime editing across various approaches and edit types.
  • La specifically enhances prime editing involving extended guide RNAs (pegRNAs) but not standard guide RNAs.
  • The engineered PE7 editor demonstrated improved prime editing efficiency with different types of pegRNAs.

Conclusions:

  • The La protein plays a critical role in promoting prime editing by interacting with pegRNAs.
  • The development of La-fused prime editors offers a strategy to enhance genome editing precision and efficiency.
  • These findings provide insights into the cellular environment's impact on exogenous small RNAs and suggest optimization strategies.