A mechanism for microRNA arm switching regulated by uridylation [AQ-seq]
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ABSTRACT:
PROVIDER: PRJNA625346 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11547029.fastq.gz | Fastqsanger.gz | |||
| SRR11547030.fastq.gz | Fastqsanger.gz | |||
| SRR11547031.fastq.gz | Fastqsanger.gz | |||
| SRR11547032.fastq.gz | Fastqsanger.gz | |||
| SRR11547033.fastq.gz | Fastqsanger.gz |
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Project description:Strand selection is a critical step in microRNA (miRNA) biogenesis. Although the dominant strand may alter depending on cellular contexts, the molecular mechanism and physiological significance of such alternative strand selection (or “arm switching”) remain elusive. Here we find miR-324 as one of the strongly regulated miRNAs by arm switching, and identify terminal uridylyl transferases TUT4 and TUT7 as the key regulators. Uridylation of pre-miR-324 by TUT4/7 re-positions DICER on the pre-miRNA and shifts the cleavage site. This alternative processing produces a duplex with a different terminus, from which the 3′ strand (3p) is selected instead of the 5′ strand (5p). In glioblastoma, the TUT4/7 and 3p levels are upregulated while the 5p level is reduced. Manipulation of the strand ratio is sufficient to impair glioblastoma cell proliferation. This study uncovers a role of uridylation as a molecular switch in alternative strand selection and implicates its therapeutic potential.
2020-04-15 | GSE148685 | GEO
Project description:Strand selection is a critical step in microRNA (miRNA) biogenesis. Although the dominant strand may alter depending on cellular contexts, the molecular mechanism and physiological significance of such alternative strand selection (or “arm switching”) remain elusive. Here we find miR-324 as one of the strongly regulated miRNAs by arm switching, and identify terminal uridylyl transferases TUT4 and TUT7 as the key regulators. Uridylation of pre-miR-324 by TUT4/7 re-positions DICER on the pre-miRNA and shifts the cleavage site. This alternative processing produces a duplex with a different terminus, from which the 3′ strand (3p) is selected instead of the 5′ strand (5p). In glioblastoma, the TUT4/7 and 3p levels are upregulated while the 5p level is reduced. Manipulation of the strand ratio is sufficient to impair glioblastoma cell proliferation. This study uncovers a role of uridylation as a molecular switch in alternative strand selection and implicates its therapeutic potential.
2020-04-15 | GSE148686 | GEO
Project description:A mechanism for microRNA arm switching regulated by uridylation
| PRJNA625342 | ENA
Project description:A mechanism for microRNA arm switching regulated by uridylation [RNA-seq]
| PRJNA625347 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-04-15 | GSE148687 | GEO
Project description:MicroRNAs (miRNAs) modulate transcript stability and translation. Functional mature miRNAs are processed from one or both arms of the hairpin precursor. The miR-100/10 family has undergone three independent evolutionary events that have switched the arm from which the functional miRNA is processed. The dominant miR-10 sequences in the insects Drosophila melanogaster and Tribolium castaneum are processed from opposite arms. However, the duplex produced by Dicer cleavage has an identical sequence in fly and beetle. Expression of the Tribolium miR-10 sequence in Drosophila S2 cells recapitulates the native beetle pattern. Thus, arm usage is encoded in the primary miRNA sequence, but outside the mature miRNA duplex. We show that the predicted messenger RNA targets and inferred function of sequences from opposite arms differ significantly. Arm switching is likely to be general, and provides a fundamental mechanism to evolve the function of a miRNA locus and target gene network.
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Project description:miRNA-seq on human fibroblast of arm For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
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Project description:Nanostring miRNA Array on human fibroblast of arm For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
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Project description:Two miRNA arms from the same precursor, miR-574-5p and miR-574-3p, were reversely expressed and played exact opposite role in gastric cancer progression. miR-574-5p/-3p ratio was also strongly correlated with higher TNM stages and shorter survival of patients. The increase of miR-574-5p/-3p ratio, or the arm-imbalance of miR-574 was due to the dynamic expression of their highly complementary targets in gastric carcinogenesis. The arm imbalance of miR-574 in turn strongly contributed to and further promoted gastric cancer progression. Conclusion: Our findings indicated that targets mediated miR-574 arm-imbalance contributed to gastric cancer progression. Re-modification of the miR-574-targets homeostasis may represent a realistic approach for gastric cancer prevention and therapy. Two miRNA arms from the same precursor, miR-574-5p and miR-574-3p, were reversely expressed and played exact opposite role in gastric cancer progression. miR-574-5p/-3p ratio was also strongly correlated with higher TNM stages and shorter survival of patients. The increase of miR-574-5p/-3p ratio, or the arm-imbalance of miR-574 was due to the dynamic expression of their highly complementary targets in gastric carcinogenesis. The arm imbalance of miR-574 in turn strongly contributed to and further promoted gastric cancer progression. Conclusion: Our findings indicated that targets mediated miR-574 arm-imbalance contributed to gastric cancer progression. Re-modification of the miR-574-targets homeostasis may represent a realistic approach for gastric cancer prevention and therapy. Two miRNA arms from the same precursor, miR-574-5p and miR-574-3p, were reversely expressed and played exact opposite role in gastric cancer progression. miR-574-5p/-3p ratio was also strongly correlated with higher TNM stages and shorter survival of patients. The increase of miR-574-5p/-3p ratio, or the arm-imbalance of miR-574 was due to the dynamic expression of their highly complementary targets in gastric carcinogenesis. The arm imbalance of miR-574 in turn strongly contributed to and further promoted gastric cancer progression. Our findings indicated that targets mediated miR-574 arm-imbalance contributed to gastric cancer progression. Re-modification of the miR-574-targets homeostasis may represent a realistic approach for gastric cancer prevention and therapy.
2019-08-25 | GSE133629 | GEO
Project description:Two miRNA arms from the same precursor, miR-574-5p and miR-574-3p, were reversely expressed and played exact opposite role in gastric cancer progression. miR-574-5p/-3p ratio was also strongly correlated with higher TNM stages and shorter survival of patients. The increase of miR-574-5p/-3p ratio, or the arm-imbalance of miR-574 was due to the dynamic expression of their highly complementary targets in gastric carcinogenesis. The arm imbalance of miR-574 in turn strongly contributed to and further promoted gastric cancer progression. Conclusion: Our findings indicated that targets mediated miR-574 arm-imbalance contributed to gastric cancer progression. Re-modification of the miR-574-targets homeostasis may represent a realistic approach for gastric cancer prevention and therapy.
2019-08-28 | GSE112859 | GEO