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Insights into function and regulation of microRNAs by decoding degradation dynamics

ABSTRACT: Insights into function and regulation of microRNAs by decoding degradation dynamics

PROVIDER: PRJNA294598 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR2230030.fastq.gz	Fastqsanger.gz
	SRR2230040.fastq.gz	Fastqsanger.gz
	SRR2230050.fastq.gz	Fastqsanger.gz
	SRR2230060.fastq.gz	Fastqsanger.gz
	SRR2230031.fastq.gz	Fastqsanger.gz

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Insights into function and regulation of microRNAs by decoding degradation dynamics [4SU]

Project description:The regulation of the miRNA pool is one of the critical events in the definition of cell identity and behavior both in steady-state condition as well during cell transitions. While mechanisms controlling biogenesis have received much attention, little is known about how miRNA are turned over, due to the lack of proper approaches to analyze miRNA decay without globally perturbing gene transcription or miRNA biogenesis. To overcome such limitations we developed a “pulse-chase” approach for the analysis of miRNA degradation dynamics at genome-wide scale in unperturbed mammalian cells. MiRNA half-lives appeared heterogeneous: while many species were very stable (T1/2 >24h, ‘slow’ miRNAs), some others are quickly turned over (T1/2 =4-14h ‘fast’ miRNAs). ‘Fast’ species comprises passenger miRNAs, as expected, and a consistent number (25/129) of guide miRNAs. These miRNAs are associated to high Target:miRNA stoichiometric ratios, particularly evident considering targets with extensive complementarity, and are enriched for 3’-end modifications (tailing and trimming), implying that target abundance and enzymatic activities are in place and mediates miRNA degradation. By integrating decay rates with biosynthetic parameters, we could model the abundance and regulation of miRNAs as a function of transcription and degradation rates and highlight how different decays could affect the magnitude and the kinetics of miRNA regulation. These findings were recapitulated in a specific biological process, namely the regulation of miRNAs by serum stimulation of quiescent fibroblast, pointing out how multiple regulatory mechanisms (synthesis, decay, target abundance and miRNA modification) concomitantly control miRNA functions.

2016-01-20 | GSE72655 | GEO

Insights into function and regulation of microRNAs by decoding degradation dynamics [serum]

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Insights into function and regulation of microRNAs by decoding degradation dynamics

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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Insights into function and regulation of microRNAs by decoding degradation dynamics

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-01-20 | GSE72656 | GEO

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Decoding Plasma Cell Maturation Dynamics with BCMA

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Transcription feedback dynamics in the wake of cytoplasmic degradation shutdown

Project description:Purpose: Studying the dynamics of the transcriptional response to acute depletion of various critical mRNA processing factors Methods: We used 4tU labeling and high-throughput polyA RNA-seq in yeast following auxin inducible degradation of key proteins. Results: We captured the detailed dynamics of cells’ adaptation to rapid degradation of Xrn1 and observed a significant accumulation of mRNA, followed by a delayed global reduction in nascent transcription and a gradual return to baseline mRNA levels. We present evidence that this transcriptional response is linked to cell cycle progression, and that it is not unique to Xrn1 depletion; rather, it is induced earlier when upstream factors in the 5'-3’ degradation pathway are perturbed. Conclusions: Our data suggest that the RNA feedback mechanism is cell-cycle-linked and monitors the accumulation of inputs to the 5’-3’ exonucleolytic pathway rather than its outputs.

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