Dataset Information

Multiple intron retention occurs in tumor cell CD44 mRNA processing.

ABSTRACT: Markedly increased overall levels of CD44 transcripts and proteins have been recognized in many tumors and the inappropriate expression and abnormal assembly of the CD44 variable exons has been linked to both tumor growth and metastatic potential. We have also previously observed the aberrant inclusion of intron 9 in CD44 mRNA transcripts in tumor tissues. In this study we assessed whether such retention is specific to certain introns or is a more general phenomenon affecting CD44 gene expression in tumor cells. Intron 18 was cloned and sequenced from genomic DNA and the novel sequences analyzed and used to create intron 18-specific probes. The newly characterized intron was found to have consensus 5' splice site and branchpoint sequences but a suboptimal 3' splice site. The status of CD44 intron 18 retention or excision was assessed in a colon tumor cell line (HT29) and in tissue from 20 colorectal tumors and matched normal mucosa. The intron was shown to be retained in transcripts from 15 of the 20 (75%) carcinomas but in only 3 of the 20 (15%) matched normal samples. These results compare with 80% retention of CD44 intron 9 in colonic carcinoma tissue mRNA and confirm that multiple abnormalities of CD44 mRNA processing occur in tumor cells.

SUBMITTER: Goodison S

PROVIDER: S-EPMC1853036 | biostudies-literature | 1998 Oct

REPOSITORIES: biostudies-literature

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Multiple intron retention occurs in tumor cell CD44 mRNA processing.

Goodison S S Yoshida K K Churchman M M Tarin D D

The American journal of pathology 19981001 4

Markedly increased overall levels of CD44 transcripts and proteins have been recognized in many tumors and the inappropriate expression and abnormal assembly of the CD44 variable exons has been linked to both tumor growth and metastatic potential. We have also previously observed the aberrant inclusion of intron 9 in CD44 mRNA transcripts in tumor tissues. In this study we assessed whether such retention is specific to certain introns or is a more general phenomenon affecting CD44 gene expressio ...[more]

PMID: 9777953

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Project description:BACKGROUND:In-depth study of the intron retention levels of transcripts provide insights on the mechanisms regulating pre-mRNA splicing efficiency. Additionally, detailed analysis of retained introns can link these introns to post-transcriptional regulation or identify aberrant splicing events in human diseases. RESULTS:We present IntEREst, Intron-Exon Retention Estimator, an R package that supports rigorous analysis of non-annotated intron retention events (in addition to the ones annotated by RefSeq or similar databases), and support intra-sample in addition to inter-sample comparisons. It accepts binary sequence alignment/map (.bam) files as input and determines genome-wide estimates of intron retention or exon-exon junction levels. Moreover, it includes functions for comparing subsets of user-defined introns (e.g. U12-type vs U2-type) and its plotting functions allow visualization of the distribution of the retention levels of the introns. Statistical methods are adapted from the DESeq2, edgeR and DEXSeq R packages to extract the significantly more or less retained introns. Analyses can be performed either sequentially (on single core) or in parallel (on multiple cores). We used IntEREst to investigate the U12- and U2-type intron retention in human and plant RNAseq dataset with defects in the U12-dependent spliceosome due to mutations in the ZRSR2 component of this spliceosome. Additionally, we compared the retained introns discovered by IntEREst with that of other methods and studies. CONCLUSION:IntEREst is an R package for Intron retention and exon-exon junction levels analysis of RNA-seq data. Both the human and plant analyses show that the U12-type introns are retained at higher level compared to the U2-type introns already in the control samples, but the retention is exacerbated in patient or plant samples carrying a mutated ZRSR2 gene. Intron retention events caused by ZRSR2 mutation that we discovered using IntEREst (DESeq2 based function) show considerable overlap with the retained introns discovered by other methods (e.g. IRFinder and edgeR based function of IntEREst). Our results indicate that increase in both the number of biological replicates and the depth of sequencing library promote the discovery of retained introns, but the effect of library size gradually decreases with more than 35 million reads mapped to the introns.

Dataset Information

Multiple intron retention occurs in tumor cell CD44 mRNA processing.

Publications

Multiple intron retention occurs in tumor cell CD44 mRNA processing.

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