Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Biallelic mutations in the 3' exonuclease TOE1 cause pontocerebellar hypoplasia and uncover a role in snRNA processing.

Nature genetics | Mar 16, 2017

Deadenylases are best known for degrading the poly(A) tail during mRNA decay. The deadenylase family has expanded throughout evolution and, in mammals, consists of 12 Mg2+-dependent 3'-end RNases with substrate specificity that is mostly unknown. Pontocerebellar hypoplasia type 7 (PCH7) is a unique recessive syndrome characterized by neurodegeneration and ambiguous genitalia. We studied 12 human families with PCH7, uncovering biallelic, loss-of-function mutations in TOE1, which encodes an unconventional deadenylase. toe1-morphant zebrafish displayed midbrain and hindbrain degeneration, modeling PCH-like structural defects in vivo. Surprisingly, we found that TOE1 associated with small nuclear RNAs (snRNAs) incompletely processed spliceosomal. These pre-snRNAs contained 3' genome-encoded tails often followed by post-transcriptionally added adenosines. Human cells with reduced levels of TOE1 accumulated 3'-end-extended pre-snRNAs, and the immunoisolated TOE1 complex was sufficient for 3'-end maturation of snRNAs. Our findings identify the cause of a neurodegenerative syndrome linked to snRNA maturation and uncover a key factor involved in the processing of snRNA 3' ends.

Pubmed ID: 28092684 RIS Download

Mesh terms: Alleles | Animals | Cerebellar Diseases | Exonucleases | Female | Humans | Male | Mice | Mutation | Neurodegenerative Diseases | Nuclear Proteins | RNA, Messenger | RNA, Small Nuclear | Spliceosomes | Zebrafish

Research resources used in this publication

None found

Research tools detected in this publication

Data used in this publication

None found

Associated grants

  • Agency: NHGRI NIH HHS, Id: UM1 HG008900
  • Agency: European Research Council, Id: 260888
  • Agency: NIGMS NIH HHS, Id: R01 GM077243
  • Agency: NHGRI NIH HHS, Id: U54 HG003067
  • Agency: NIGMS NIH HHS, Id: R35 GM118069
  • Agency: NINDS NIH HHS, Id: P30 NS047101
  • Agency: NIGMS NIH HHS, Id: F32 GM106706
  • Agency: NINDS NIH HHS, Id: R01 NS050375
  • Agency: NINDS NIH HHS, Id: R01 NS041537
  • Agency: NINDS NIH HHS, Id: R01 NS048453
  • Agency: NIGMS NIH HHS, Id: T32 GM007240
  • Agency: NHGRI NIH HHS, Id: U54 HG006504
  • Agency: NHGRI NIH HHS, Id: R01 HG004659
  • Agency: NICHD NIH HHS, Id: K99 HD082337
  • Agency: NINDS NIH HHS, Id: R01 NS052455
  • Agency: NICHD NIH HHS, Id: P01 HD070494
  • Agency: NINDS NIH HHS, Id: R01 NS098004
  • Agency: NHGRI NIH HHS, Id: UM1 HG006493
  • Agency: NINDS NIH HHS, Id: R01 NS058721
  • Agency: NINDS NIH HHS, Id: R01 NS075449

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


Ambion Inc.

A division of Applied Biosystems selling products for the isolation, detection, quantification, amplification, and characterization of RNA.

tool

View all literature mentions

OMIM

Collection of human genes and genetic phenotypes, focusing on the relationship between phenotype and genotype. The full-text, referenced overviews in OMIM contain information on all known mendelian disorders and a variety of related genes. It is updated daily, and the entries contain copious links to other genetics resources.

tool

View all literature mentions

NHLBI Exome Sequencing Project (ESP)

The goal of the project is to discover novel genes and mechanisms contributing to heart, lung and blood disorders by pioneering the application of next-generation sequencing of the protein coding regions of the human genome across diverse, richly-phenotyped populations and to share these datasets and findings with the scientific community to extend and enrich the diagnosis, management and treatment of heart, lung and blood disorders. The groups participating and collaborating in the NHLBI GO ESP include: Seattle GO - University of Washington, Seattle, WA Broad GO - Broad Institute of MIT and Harvard, Cambridge, MA WHISP GO - Ohio State University Medical Center, Columbus, OH Lung GO - University of Washington, Seattle, WA WashU GO - Washington University, St. Louis, MO Heart GO - University of Virginia Health System, Charlottesville, VA ChargeS GO - University of Texas Health Sciences Center at Houston

tool

View all literature mentions

Covance

A contract research organization providing drug development and animal testing services. Under the name Covance Research Products Inc., based in Denver, Pennsylvania, the company also deals in the import, breeding and sale of laboratory animals. It breeds dogs, rabbits, guinea pigs, non-human primates, and pigs, and runs the largest non-human primate laboratory in Germany. (Wikipedia)

tool

View all literature mentions

Bioconductor

Software repository for R packages related to analysis and comprehension of high throughput genomic data. Uses separate set of commands for installation of packages. Software project based on R programming language that provides tools for analysis and comprehension of high throughput genomic data.

tool

View all literature mentions