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Related Concept Videos

lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

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In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
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Types of RNA01:20

Types of RNA

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Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in regulating gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA Performs Diverse...
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piRNA - Piwi-interacting RNAs02:57

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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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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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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.
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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.
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RNA Pull-down Procedure to Identify RNA Targets of a Long Non-coding RNA
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Structural features within the NORAD long noncoding RNA underlie efficient repression of Pumilio activity.

Svetlana Farberov1, Omer Ziv2,3, Jian You Lau4

  • 1Department of Immunology and Regenerative Biology and Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel.

Nature Structural & Molecular Biology
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Long noncoding RNAs (lncRNAs) have modular structures that dictate their functions. Researchers revealed NORAD lncRNA

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Area of Science:

  • Molecular Biology
  • Genomics
  • RNA Biology

Background:

  • Long noncoding RNAs (lncRNAs) play crucial roles in mammalian cells, but their structure-function relationships are poorly understood.
  • The NORAD lncRNA acts as a decoy for Pumilio proteins, influencing mRNA regulation, genomic stability, and aging.
  • Understanding lncRNA structural principles is key to deciphering their regulatory mechanisms and designing novel RNA therapeutics.

Purpose of the Study:

  • To investigate the structural organization and RNA-RNA interactions of human NORAD under cellular stress.
  • To elucidate how NORAD's structure spatially clusters Pumilio binding sites and influences gene expression.
  • To apply these structural insights for the rational design of artificial lncRNA decoys.

Main Methods:

  • In-cell probing of RNA structure and long-range RNA-RNA interactions.
  • Analysis of NORAD structure and interactions under arsenite-induced stress.
  • Computational and experimental design of artificial RNA decoys.

Main Results:

  • NORAD exhibits a modular structure with independently functioning domains.
  • Arsenite stress induces structural relaxation and stress granule targeting of NORAD.
  • NORAD's unique structure clusters Pumilio binding sites, leading to derepression of Pumilio targets.
  • Designed artificial decoys demonstrated effective modulation of microRNA activity.

Conclusions:

  • lncRNA sequence dictates spatial clustering of function into distinct domains.
  • Structural principles of lncRNAs can be leveraged for the rational design of functional RNA molecules.
  • This study provides a framework for understanding lncRNA structure-function and designing RNA-based tools.