Dec 3, 2013

U2AF1 mutations alter splice site recognition in hematological malignancies

BioRxiv : the Preprint Server for Biology
Janine O IlaganRobert K Bradley

Abstract

Whole-exome sequencing studies have identified common mutations affecting genes encoding components of the RNA splicing machinery in hematological malignancies; however, the molecular consequences of these mutations are unknown. Here, we synthesize patient data, cell culture experiments, and structural modeling to systematically determine how mutations affecting the 3′ splice site recognition factor U2AF1 alter its normal role in RNA splicing in myeloid malignancies. In contrast to initial reports that U2AF1 mutations cause loss of function and global splicing failure, we find that these U2AF1 mutations instead cause gain of function to promote or repress specific variants of the consensus 3′ splice site. Mutations affecting the first and second zinc fingers give rise to different alterations in splice site preference, which influence the similarity of splicing programs in tumors. These allele-specific effects are consistent with a computationally predicted model of U2AF1 in complex with RNA. We created comprehensive global maps of differential splicing driven by each U2AF1 mutation, and use these maps to identify genes that are consistently affected by U2AF1 mutations both in vivo and in cell culture. Many such genes participa...Continue Reading

  • References
  • Citations

References

  • We're still populating references for this paper, please check back later.
  • References
  • Citations

Citations

  • This paper may not have been cited yet.

Mentioned in this Paper

DNMT3B
U2AF1
Zinc Fingers
In Vivo
Pathogenic Aspects
Biochemical Pathway
DNA Methylation [PE]
Pathogenesis
Hematologic Neoplasms
Genes

About this Paper

Related Feeds

Cancer Epigenetics & Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.

Cancer Genomics (Preprints)

Cancer genomics employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest preprints here.

Cancer Epigenetics and Senescence (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may be involved in regulating senescence in cancer cells. This feed captures the latest research on cancer epigenetics and senescence.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.

Cancer Epigenetics & Methyl-CpG (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. Here is the latest research on cancer epigenetics and methyl-CpG binding proteins including ZBTB38.

Cancer Epigenetics

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Cell Signaling & Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. This feed covers the latest research on signaling and epigenetics in cell growth and cancer.

Related Papers

ContactHelpTerms Privacy Cookies Blog
© 2020 Meta ULC. All rights reserved