Dataset Information

The human TUT1 nucleotidyl transferase as a global regulator of microRNA abundance.

ABSTRACT: Post-transcriptional modifications of miRNAs with 3' non-templated nucleotide additions (NTA) are a common phenomenon, and for a handful of miRNAs the additions have been demonstrated to modulate miRNA stability. However, it is unknown for the vast majority of miRNAs whether nucleotide additions are associated with changes in miRNA expression levels. We previously showed that miRNA 3' additions are regulated by multiple nucleotidyl transferase enzymes. Here we examine the changes in abundance of miRNAs that exhibit altered 3' NTA following the suppression of a panel of nucleotidyl transferases in cancer cell lines. Among the miRNAs examined, those with increased 3' additions showed a significant decrease in abundance. More specifically, miRNAs that gained a 3' uridine were associated with the greatest decrease in expression, consistent with a model in which 3' uridylation influences miRNA stability. We also observed that suppression of one nucleotidyl transferase, TUT1, resulted in a global decrease in miRNA levels of approximately 40% as measured by qRT-PCR-based miRNA profiling. The mechanism of this global miRNA suppression appears to be indirect, as it occurred irrespective of changes in 3' nucleotide addition. Also, expression of miRNA primary transcripts did not decrease following TUT1 knockdown, indicating that the mechanism is post-transcriptional. In conclusion, our results suggest that TUT1 affects miRNAs through both a direct effect on 3' nucleotide additions to specific miRNAs and a separate, indirect effect on miRNA abundance more globally.

SUBMITTER: Knouf EC

PROVIDER: S-EPMC3715485 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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The human TUT1 nucleotidyl transferase as a global regulator of microRNA abundance.

Knouf Emily C EC Wyman Stacia K SK Tewari Muneesh M

PloS one 20130718 7

Post-transcriptional modifications of miRNAs with 3' non-templated nucleotide additions (NTA) are a common phenomenon, and for a handful of miRNAs the additions have been demonstrated to modulate miRNA stability. However, it is unknown for the vast majority of miRNAs whether nucleotide additions are associated with changes in miRNA expression levels. We previously showed that miRNA 3' additions are regulated by multiple nucleotidyl transferase enzymes. Here we examine the changes in abundance of ...[more]

PMID: 23874977

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Project description:BACKGROUND: Recently, microRNAs (miRNAs) have taken centre stage in the field of human molecular oncology. Several studies have shown that miRNA profiling analyses offer new possibilities in cancer classification, diagnosis and prognosis. However, the function of miRNAs that are dysregulated in tumours remains largely a mystery. Global analysis of miRNA-target gene expression has helped illuminate the role of miRNAs in developmental gene expression programs, but such an approach has not been reported in cancer transcriptomics. RESULTS: In this study, we globally analysed the expression patterns of miRNA target genes in prostate cancer by using several public microarray datasets. Intriguingly, we found that, in contrast to global mRNA transcript levels, putative miRNA targets showed a reduced abundance in prostate tumours relative to benign prostate tissue. Additionally, the down-regulation of these miRNA targets positively correlated with the number of types of miRNA target-sites in the 3' untranslated regions of these targets. Further investigation revealed that the globally low expression was mainly driven by the targets of 36 specific miRNAs that were reported to be up-regulated in prostate cancer by a miRNA expression profiling study. We also found that the transcript levels of miRNA targets were lower in androgen-independent prostate cancer than in androgen-dependent prostate cancer. Moreover, when the global analysis was extended to four other cancers, significant differences in transcript levels between miRNA targets and total mRNA backgrounds were found. CONCLUSION: Global gene expression analysis, along with further investigation, suggests that miRNA targets have a significantly reduced transcript abundance in prostate cancer, when compared with the combined pool of all mRNAs. The abnormal expression pattern of miRNA targets in human cancer could be a common feature of the human cancer transcriptome. Our study may help to shed new light on the functional roles of miRNAs in cancer transcriptomics.

Dataset Information

The human TUT1 nucleotidyl transferase as a global regulator of microRNA abundance.

Publications

The human TUT1 nucleotidyl transferase as a global regulator of microRNA abundance.

Similar Datasets

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