Gene Expression Nebulas
A data portal of transcriptomic profiles analyzed by a unified pipeline across multiple species

Gene Expression Nebulas

A data portal of transcriptome profiles across multiple species
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PRJNA295064

PRJNA295064: Cancer associated SF3B1 hotspot mutations induce cryptic 3' splice site selection through use of a different branch point

Source: NCBI / GSE072790
Submission Date: Sep 08 2015
Release Date: Sep 08 2015
Update Date: May 15 2019

Summary: Recurrent mutations in the spliceosome are observed in several human cancers but their functional and therapeutic significance remain elusive. SF3B1, the most frequently mutated component of the spliceosome in cancer, is involved in the recognition of the branch point sequence (BPS) during selection of the 3’ splice site (ss) in RNA splicing. Here, we report that common and tumor-specific splicing aberrations are induced by SF3B1 mutations and establish aberrant 3’ ss selection as the most frequent splicing defect. Strikingly, mutant SF3B1 utilizes a BPS that differs from that used by wild-type SF3B1 and requires the canonical 3’ ss to enable aberrant splicing during the second step. Approximately 50% of the aberrantly spliced mRNAs are subjected to nonsense-mediated decay resulting in downregulation of gene and protein expression. These findings ascribe functional significance to the consequences of SF3B1 mutations in cancer.

Overall Design: 66 samples, including two sets of patient data and cell lines with two additional technical replicates each

GEN Datasets:
GEND000003
Strategy:
Species:
Tissue:
Healthy Condition:
Cell Type:
Cell Line:
Protocol
Growth Protocol: -
Treatment Protocol: -; cycloheximide (+CHX)
Extract Protocol: Total RNA was harvested and Poly A selected
Library Construction Protocol: RNA libraries were prepared for sequencing using standard Illumina protocols
Sequencing
Molecule Type: poly(A)+ RNA
Library Source:
Library Layout: PAIRED
Library Strand: -; Forward
Platform: ILLUMINA
Instrument Model: Illumina HiSeq 2000
Strand-Specific: Unspecific; Specific
Samples
Basic Information:
Sample Characteristic:
Biological Condition:
Experimental Variables:
Protocol:
Sequencing:
Assessing Quality:
Analysis:
Data Resource GEN Sample ID GEN Dataset ID Project ID BioProject ID Sample ID Sample Name BioSample ID Sample Accession Experiment Accession Release Date Submission Date Update Date Species Race Ethnicity Age Age Unit Gender Source Name Tissue Cell Type Cell Subtype Cell Line Disease Disease State Development Stage Mutation Phenotype Case Detail Control Detail Growth Protocol Treatment Protocol Extract Protocol Library Construction Protocol Molecule Type Library Layout Strand-Specific Library Strand Spike-In Strategy Platform Instrument Model Cell Number Reads Number Gbases AvgSpotLen1 AvgSpotLen2 Uniq Mapping Rate Multiple Mapping Rate Coverage Rate
Publications
Cancer-Associated SF3B1 Hotspot Mutations Induce Cryptic 3' Splice Site Selection through Use of a Different Branch Point.
Cell reports . 2015-10-22 [PMID: 26565915]
Hemopoietic-specific Sf3b1-K700E knock-in mice display the splicing defect seen in human MDS but develop anemia without ring sideroblasts.
Leukemia . 2016-09-08 [PMID: 27604819]
The K666N mutation in SF3B1 is associated with increased progression of MDS and distinct RNA splicing.
Blood advances . 2020-04-01 [PMID: 32211880]