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Related Concept Videos

RNA Splicing01:32

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
RNA Splicing01:32

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
Alternative RNA Splicing02:18

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
Pre-mRNA Processing: RNA Splicing01:32

Pre-mRNA Processing: RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
Alternative RNA Splicing02:18

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...

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DROSHA targets its own transcript to modulate alternative splicing.

Dooyoung Lee1, Jin-Wu Nam2, Chanseok Shin1,3,4

  • 1Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea.

RNA (New York, N.Y.)
|April 13, 2017
PubMed
Summary
This summary is machine-generated.

The DROSHA enzyme targets its own transcript, influencing gene splicing. This discovery reveals a novel noncanonical function for DROSHA beyond microRNA processing.

Keywords:
DROSHAMicroprocessoralternative splicing

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Area of Science:

  • Molecular Biology
  • Gene Regulation
  • RNA Processing

Background:

  • The Microprocessor complex, comprising DROSHA and DGCR8, processes microRNAs (miRNAs).
  • DROSHA also cleaves non-miRNA hairpins, a function less understood.
  • The regulation of DROSHA's own gene expression is largely unexplored.

Purpose of the Study:

  • To investigate noncanonical functions of the DROSHA enzyme.
  • To identify and characterize the regulatory role of DROSHA on its own transcript.
  • To elucidate the mechanism by which DROSHA influences alternative splicing of its gene.

Main Methods:

  • Bioinformatic analysis of mammalian DROSHA gene sequences.
  • In vitro assays to assess Microprocessor complex activity.
  • RNA sequencing and splicing analysis in human cell lines.
  • CRISPR-Cas9 gene editing to study DROSHA function.

Main Results:

  • A conserved hairpin structure in the human DROSHA transcript serves as a Microprocessor substrate.
  • This hairpin element dictates alternative versus constitutive splicing of an overlapping exon.
  • DROSHA promotes exon skipping in a cleavage-independent manner in human cells.
  • The observed hairpin and regulatory mechanism are specific to human, not murine, DROSHA genes.

Conclusions:

  • The human DROSHA transcript is a noncanonical target of the Microprocessor complex.
  • DROSHA autoregulation involves a conserved hairpin structure influencing its own alternative splicing.
  • These findings expand the known repertoire of DROSHA's functions beyond canonical miRNA biogenesis.