Related Experiment Video

Updated: Dec 7, 2025

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
09:34

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

34.4K

Human disease-associated single nucleotide polymorphism changes the orientation of DROSHA on pri-mir-146a

Cong Truc Le1, Thuy Linh Nguyen1, Trung Duc Nguyen1

  • 1Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China.

RNA (New York, N.Y.)
|September 30, 2020
PubMed

Insights

A disease-associated single nucleotide polymorphism (SNP) in pri-mir-146a alters Microprocessor complex binding, leading to unproductive miRNA processing and reduced miRNA expression.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • MicroRNAs (miRNAs) are crucial regulators of gene expression, synthesized via a process initiated by the Microprocessor complex.
  • The Microprocessor complex, comprising DROSHA and DGCR8, processes primary miRNAs (pri-miRNAs) into precursor miRNAs.
  • Microprocessor orientation on pri-miRNAs determines productive (miRNA-generating) or unproductive cleavage.

Purpose of the Study:

  • To investigate the molecular mechanism by which a disease-associated single nucleotide polymorphism (SNP, rs2910164) in pri-mir-146a affects miRNA biosynthesis.
  • To determine if the SNP directly impacts Microprocessor activity and its orientation on pri-mir-146a.

Main Methods:

  • Analysis of pri-mir-146a structure and Microprocessor complex interactions.
  • Investigating the effect of the SNP on Microprocessor binding orientation and cleavage activity.

Main Results:

  • The SNP (rs2910164) in pri-mir-146a creates an mGHG motif at the apical junction.
  • This mGHG motif interacts with the DROSHA double-stranded RNA-binding domain (dsRBD).
  • The interaction switches Microprocessor orientation to the apical junction, favoring unproductive cleavage.

Conclusions:

  • The disease-associated SNP in pri-mir-146a directly modulates Microprocessor activity by altering its binding site.
  • This leads to a shift towards unproductive cleavage, impacting miRNA biogenesis and cellular function.
  • Elucidates the molecular basis for SNP-associated human diseases linked to pri-mir-146a.
Keywords:
DGCR8DROSHAmiR-146amiRNArs2910164single nucleotide polymorphism

More Related Videos

Removal of an Internal Translational Start Site from mRNA While Retaining Expression of the Full-Length Protein05:48

Removal of an Internal Translational Start Site from mRNA While Retaining Expression of the Full-Length Protein

Published on: March 16, 2022

2.9K
Probing RNA Structure with Dimethyl Sulfate Mutational Profiling with Sequencing In Vitro and in Cells10:34

Probing RNA Structure with Dimethyl Sulfate Mutational Profiling with Sequencing In Vitro and in Cells

Published on: December 9, 2022

4.9K

Related Concept Videos

Single Nucleotide Polymorphisms-SNPs01:05

Single Nucleotide Polymorphisms-SNPs

A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
17.6K
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.5K
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...
3.5K
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...
23.5K
RNA Editing02:23

RNA Editing

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...
9.6K
piRNA - Piwi-interacting RNAs02:57

piRNA - Piwi-interacting RNAs

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...
7.3K