Related Experiment Video
Updated: Jun 3, 2025
07:08
Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
Published on: February 27, 2018
9.5K
DUX4-induced HSATII RNA accumulation drives protein aggregation impacting RNA processing pathways
Tessa Arends1, Sean R Bennett1, Stephen J Tapscott1,2,3
1Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA 98109.
Biorxiv : the Preprint Server for Biology
|January 7, 2025
Summary
Double homeobox 4 (DUX4) causes stable intranuclear RNA accumulation, driving protein aggregation and cellular issues in facioscapulohumeral muscular dystrophy (FSHD). HSATII RNA plays a key role in regulating RNA processing and DUX4-mediated disease mechanisms.
Area of Science:
- Molecular Biology
- Genetics
- Cellular Biology
Background:
- RNA-driven protein aggregation contributes to disease and tumorigenesis.
- Double homeobox 4 (DUX4) is implicated in facioscapulohumeral muscular dystrophy (FSHD).
Purpose of the Study:
- To investigate how DUX4 influences nuclear RNA dynamics and protein aggregation.
- To elucidate the role of human satellite II (HSATII) RNA in DUX4-mediated cellular dysregulation.
Main Methods:
- Analysis of intranuclear RNA accumulation in DUX4-expressing cells.
- Investigation of HSATII RNA interactions with RNA methylation factors and YBX1.
- Assessment of RNA splicing alterations due to HSATII-RNP complexes.
Main Results:
- DUX4 induces accumulation of stable intranuclear RNAs, including HSATII RNA.
- HSATII RNA sequesters RNA methylation factors, forming HSATII-YBX1 ribonucleoprotein (RNP) complexes.
- Aberrant HSATII-RNP complexes lead to differential gene splicing, impacting DUX4-dysregulated pathways.
Conclusions:
- DUX4 significantly impacts nuclear RNA dynamics, with HSATII RNA acting as a critical mediator.
- HSATII-RNP complex formation influences RNA processing pathways, offering insights into FSHD pathogenesis.
Related Concept Videos
02:28Leaky Scanning
5.1K
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...
5.1K
02:15Experimental RNAi
6.0K
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...
6.0K
02:30siRNA - Small Interfering RNAs
16.6K
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...
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...
16.6K
02:41Chromatin Structure Regulates pre-mRNA Processing
6.9K
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...
The chromatin structure, especially...
6.9K
01:31Translation
14.5K
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Proteins are...
Translation Produces the Building Blocks of Life
Proteins are...
14.5K
02:23RNA Editing
8.9K
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...
8.9K