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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...
Small interfering RNAs (siRNA)02:30

Small interfering RNAs (siRNA)

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 ATP-dependent...
RNA Stability01:53

RNA Stability

Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
RNA Stability01:53

RNA Stability

Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...

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Weak seed-pairing stability and high target-site abundance decrease the proficiency of lsy-6 and other microRNAs.

David M Garcia1, Daehyun Baek, Chanseok Shin

  • 1Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA.

Nature Structural & Molecular Biology
|September 13, 2011
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Nematode lsy-6 microRNA (miRNA) and mammalian miR-23 show low gene repression proficiency due to weak seed-pairing stability and high target-site abundance. This finding improves prediction tools for miRNA and small interfering RNA (siRNA) regulation.

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Published on: September 28, 2011

Area of Science:

  • Molecular Biology
  • Genetics
  • Bioinformatics

Background:

  • Most microRNAs (miRNAs) regulate numerous genes, but some exhibit limited proficiency.
  • The nematode lsy-6 miRNA is known for its low gene repression efficiency.

Purpose of the Study:

  • To investigate the factors contributing to the low proficiency of lsy-6 miRNA.
  • To determine if mammalian miRNAs also exhibit low proficiency and identify associated properties.
  • To enhance computational tools for predicting miRNA and small interfering RNA (siRNA) regulation.

Main Methods:

  • Recapitulating lsy-6 miRNA function in HeLa cells.
  • Utilizing reporter assays and array data to analyze miRNA properties.
  • Expanding the TargetScan algorithm to model miRNA and siRNA proficiencies.

Main Results:

  • The low proficiency of lsy-6 miRNA was successfully replicated in mammalian cells.
  • Weak predicted seed-pairing stability (SPS) and high target-site abundance (TA) were identified as key factors for low miRNA proficiency.
  • These properties also explain differential off-target effects of siRNAs.
  • The enhanced TargetScan tool showed improved prediction performance for miRNA and siRNA regulation.

Conclusions:

  • Low miRNA proficiency is linked to weak SPS and high TA.
  • Understanding these properties can guide the design of more specific siRNAs with reduced off-target activity.
  • The refined TargetScan tool offers better quantitative prediction of small RNA regulation.