Dataset Information

Sequencing of Argonaute-bound microRNA/mRNA hybrids reveals regulation of the unfolded protein response by microRNA-320a.

ABSTRACT: MicroRNAs (miRNA) are short non-coding RNAs widely implicated in gene regulation. Most metazoan miRNAs utilize the RNase III enzymes Drosha and Dicer for biogenesis. One notable exception is the RNA polymerase II transcription start sites (TSS) miRNAs whose biogenesis does not require Drosha. The functional importance of the TSS-miRNA biogenesis is uncertain. To better understand the function of TSS-miRNAs, we applied a modified Crosslinking, Ligation, and Sequencing of Hybrids on Argonaute (AGO-qCLASH) to identify the targets for TSS-miRNAs in HCT116 colorectal cancer cells with or without DROSHA knockout. We observed that miR-320a hybrids dominate in TSS-miRNA hybrids identified by AGO-qCLASH. Targets for miR-320a are enriched for the eIF2 signaling pathway, a downstream component of the unfolded protein response. Consistently, in miR-320a mimic- and antagomir- transfected cells, differentially expressed gene products are associated with eIF2 signaling. Within the AGO-qCLASH data, we identified the endoplasmic reticulum (ER) chaperone calnexin as a direct miR-320a down-regulated target, thus connecting miR-320a to the unfolded protein response. During ER stress, but not amino acid deprivation, miR-320a up-regulates ATF4, a critical transcription factor for resolving ER stress. In summary, our study investigates the targetome of the TSS-miRNAs in colorectal cancer cells and establishes miR-320a as a regulator of unfolded protein response.

SUBMITTER: Fields CJ

PROVIDER: S-EPMC8675727 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Sequencing of Argonaute-bound microRNA/mRNA hybrids reveals regulation of the unfolded protein response by microRNA-320a.

Fields Christopher J CJ Li Lu L Hiers Nicholas M NM Li Tianqi T Sheng Peike P Huda Taha T Shan Jixiu J Gay Lauren L Gu Tongjun T Bian Jiang J Kilberg Michael S MS Renne Rolf R Xie Mingyi M

PLoS genetics 20211216 12

MicroRNAs (miRNA) are short non-coding RNAs widely implicated in gene regulation. Most metazoan miRNAs utilize the RNase III enzymes Drosha and Dicer for biogenesis. One notable exception is the RNA polymerase II transcription start sites (TSS) miRNAs whose biogenesis does not require Drosha. The functional importance of the TSS-miRNA biogenesis is uncertain. To better understand the function of TSS-miRNAs, we applied a modified Crosslinking, Ligation, and Sequencing of Hybrids on Argonaute (AGO ...[more]

PMID: 34914716

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Project description:Geloina erosa is an important benthic animal in the mangrove, serving as an indicator organism for coastal environmental pollution. This study aimed to investigate the tissue-specific expression of miRNAs and their regulatory roles in predicted targets in G. erosa. Through miRNA sequencing and co-expression network analysis, we extensively studied the miRNA expression in three tissues: gills, hepatopancreas, and muscle. The results revealed a total of 1412 miRNAs, comprising 1047 known miRNAs, and 365 newly predicted miRNAs. These miRNAs exhibited distinct tissue-specific expression patterns. In the miRNA target gene prediction, a total of 7404 potential predicted targets were identified, representing approximately 33% of all unique transcripts associated with miRNAs. Further co-expression network analysis revealed nine modules, each showing a positive correlation with specific tissues (gills, hepatopancreas, or muscle). The blue module showed a significant correlation with gills (r = 0.83, p-value = 0.006), the black module was significantly related to the hepatopancreas (r = 0.78, p-value = 0.01), and the purple module was significantly correlated with muscle (r = 0.83, p-value = 0.006). Within these modules, related miRNAs tended to cluster together, while their correlations with other modules were relatively weak. Functional enrichment analysis was performed on miRNAs and their predicted targets in each tissue. In the gills, miRNAs primarily regulate immune-related genes, substance transport, and cytoskeletal organization. In the hepatopancreas, miRNAs suppressed genes involved in shell formation and played a role in cellular motor activity and metabolism. In muscle, miRNAs participate in metabolism and photoreceptive processes, as well as immune regulation. In summary, this study provides valuable insights into the tissue-specific regulation of miRNAs in G. erosa, highlighting their potential roles in immune response, metabolism, and environmental adaptation. These findings offer important clues for understanding the molecular mechanisms and biological processes in G. erosa, laying the foundation for further validation and elucidation of these regulatory relationships.

Dataset Information

Sequencing of Argonaute-bound microRNA/mRNA hybrids reveals regulation of the unfolded protein response by microRNA-320a.

Publications

Sequencing of Argonaute-bound microRNA/mRNA hybrids reveals regulation of the unfolded protein response by microRNA-320a.

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