Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A ubiquitin ligase mediates target-directed microRNA decay independently of tailing and trimming [TDMD]

ABSTRACT: MicroRNAs (miRNAs) act in concert with Argonaute (AGO) proteins to broadly repress mRNA targets. After AGO loading, miRNAs generally exhibit slow turnover. An important exception occurs when miRNAs encounter targets with extensive complementarity, which can trigger a process termed target-directed microRNA degradation (TDMD). Prevailing models of TDMD invoke miRNA tailing and trimming as an essential step in the decay mechanism. Here, a genome-wide screen revealed a novel cullin-RING ubiquitin ligase, which we named the DECAY complex, that mediates TDMD. The DECAY complex interacts with AGO proteins, mediates TDMD induced by multiple transcripts, and does not require tailing and trimming to elicit miRNA turnover. Based upon these findings, we propose a model in which the DECAY complex mediates TDMD by promoting proteasomal decay of miRNA-containing complexes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE151516 | GEO | 2020/11/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

A ubiquitin ligase mediates target-directed microRNA decay independently of tailing and trimming [small RNA-seq]

Project description:MicroRNAs (miRNAs) act in concert with Argonaute (AGO) proteins to broadly repress mRNA targets. After AGO loading, miRNAs generally exhibit slow turnover. An important exception occurs when miRNAs encounter targets with extensive complementarity, which can trigger a process termed target-directed microRNA degradation (TDMD). Prevailing models of TDMD invoke miRNA tailing and trimming as an essential step in the decay mechanism. Here, a genome-wide screen revealed a novel cullin-RING ubiquitin ligase, which we named the DECAY complex, that mediates TDMD. The DECAY complex interacts with AGO proteins, mediates TDMD induced by multiple transcripts, and does not require tailing and trimming to elicit miRNA turnover. Based upon these findings, we propose a model in which the DECAY complex mediates TDMD by promoting proteasomal decay of miRNA-containing complexes.

2020-11-13 | GSE158025 | GEO

A ubiquitin ligase mediates target-directed microRNA decay independently of tailing and trimming [miRNA-seq]

2020-11-13 | GSE151396 | GEO

Widespread destabilization of C. elegans microRNAs by the E3 ubiquitin ligase EBAX-1 [RNA-Seq]

Project description:MicroRNAs (miRNAs) associate with Argonaute (AGO) proteins to form a complex that directs mRNA repression. One way that miRNAs are regulated is at the level of their stability. Some animal miRNAs are destabilized through a pathway in which pairing to specialized RNA transcripts recruits the ZSWIM8 E3 ubiquitin ligase, which polyubiquitinates AGO, leading to its degradation and exposure of the miRNA to cellular nucleases. We found that 22 miRNAs in C. elegans are sensitive to loss of EBAX-1, the ZSWIM8 ortholog in nematodes, implying that these 22 miRNAs might be subject to this pathway of target-directed miRNA degradation (TDMD). These miRNAs included the embryonic miR-35–42 family, as well as other miRNAs among the least stable in the worm, suggesting that TDMD is a major pathway of miRNA destabilization in the worm. The excess miR-35–42 molecules that accumulated in ebax-1 mutants caused increased repression of their predicted target mRNAs and underwent 3′ trimming over time. In general, however, miRNAs sensitive to loss of EBAX-1 did not have a consistent pattern of either trimming or tailing. A previous study reports that in contrast to TDMD substrates in mammals and flies, the 3′ region of miR-35 is not required for its destabilization, raising the question of whether the 3′ regions of other miRNAs are dispensable for EBAX-1 sensitivity in nematodes. To address this question, we replaced the 3′ region of another EBAX-sensitive miRNA, miR-43, and found that this replacement greatly reduced EBAX-sensitivity in the worm. Together, these findings broaden the implied biological scope of TDMD-like regulation of miRNA stability in animals, and indicate that the requirement for miRNA 3′ sequences in this process is variable in the worm.

2024-11-04 | GSE267368 | GEO

Widespread destabilization of C. elegans microRNAs by the E3 ubiquitin ligase EBAX-1 [miRNA-Seq]

2024-11-04 | GSE267367 | GEO

A ubiquitin ligase mediates target-directed microRNA decay independently of tailing and trimming [TDMD]

Project description:A ubiquitin ligase mediates target-directed microRNA decay independently of tailing and trimming [TDMD]

| PRJNA636178 | ENA

The ZSWIM8 ubiquitin ligase mediates target-directed microRNA degradation [dataset 2]

Project description:MicroRNAs (miRNAs) associate with Argonaute (AGO) proteins to direct widespread post-transcriptional gene repression. Although association with AGO typically protects miRNAs from nucleases, extensive pairing to some unusual target RNAs can trigger miRNA degradation. Here we found that this target-directed miRNA degradation (TDMD) required the ZSWIM8 Cullin-RING E3 ubiquitin ligase. This and other findings suggested and supported a mechanistic model of TDMD in which target-directed proteolysis of AGO by the ubiquitin–proteasome pathway exposes the miRNA for degradation. Moreover, loss-of-function studies indicated that the ZSWIM8 Cullin-RING ligase accelerates degradation of numerous miRNAs in cells of mammals, flies, and nematodes, thereby specifying the half-lives of most short-lived miRNAs. These results elucidate the mechanism of TDMD and expand the inferred role of TDMD in shaping miRNA levels in bilaterian animals.

2020-12-18 | GSE163387 | GEO

The ZSWIM8 ubiquitin ligase mediates target-directed microRNA degradation [dataset 1]

2020-12-18 | GSE163393 | GEO

The ZSWIM8 ubiquitin ligase mediates target-directed microRNA degradation [dataset3]

2020-12-18 | GSE163388 | GEO

The ZSWIM8 ubiquitin ligase mediates target-directed microRNA degradation [datatset 7]

2020-12-18 | GSE163392 | GEO

The ZSWIM8 ubiquitin ligase mediates target-directed microRNA degradation [dataset 6]

2020-12-18 | GSE163391 | GEO