scholarly journals A non-canonical microRNA derived from the snaR-A non-coding RNA targets a metastasis inhibitor

RNA ◽  
2021 ◽  
pp. rna.078694.121
Author(s):  
Daniel Stribling ◽  
Yi Lei ◽  
Casey M. Guardia ◽  
Lu Li ◽  
Christopher J. Fields ◽  
...  
2021 ◽  
Author(s):  
Daniel Stribling ◽  
Yi Lei ◽  
Casey M Guardia ◽  
Lu Li ◽  
Christopher J Fields ◽  
...  

MicroRNAs (miRNAs) are small noncoding RNAs that function as critical post-transcriptional regulators in various biological processes. While most miRNAs are generated from processing of long primary transcripts via sequential Drosha and Dicer cleavage, some miRNAs that bypass Drosha cleavage can be transcribed as part of another small non-coding RNA. Here, we develop the Target-Oriented miRNA Discovery (TOMiD) bioinformatic analysis method to identify Drosha-independent miRNAs from Argonaute crosslinking and sequencing of hybrids (Ago-CLASH) datasets. Using this technique, we discovered a novel miRNA derived from a primate specific non-coding RNA, the small NF90 associated RNA A (snaR-A). The miRNA derived from snaR-A (miR-snaR) arises independent of Drosha processing, but requires Exportin-5 and Dicer for biogenesis. We identify that miR-snaR is concurrently upregulated with the full snaR-A transcript in cancer cells. Functionally, miR-snaR associates with Ago proteins and targets NME1, a key metastasis inhibitor, contributing to snaR-A's role in promoting cancer cell migration. Our findings suggest a functional link between a novel miRNA and its precursor non-coding RNA.


2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Chia-Yu Chung ◽  
Amit Berson ◽  
Jason R. Kennerdell ◽  
Ashley Sartoris ◽  
Travis Unger ◽  
...  

2018 ◽  
Vol 123 (3) ◽  
pp. 469-482 ◽  
Author(s):  
Tongtong Yu ◽  
David T W Tzeng ◽  
Ran Li ◽  
Jianye Chen ◽  
Silin Zhong ◽  
...  

2020 ◽  
Author(s):  
Audrey Jacq ◽  
Denis Becquet ◽  
Séverine Guillen ◽  
Bénédicte Boyer ◽  
Maria-Montserrat Bello-Goutierrez ◽  
...  

ABSTRACTParaspeckles are nuclear ribonucleic complex formed of a long non-coding RNA, nuclear-enriched abundant transcript one (Neat1) and associated RNA-binding proteins (RBP) whose cellular known functions are to sequester in the nucleus both proteins and RNAs. However, how RNAs are bound to paraspeckles is largely unknown. It is highly likely that binding of RNAs may occur via interactions with RBPs and accordingly, two structures present in the 3’UTR of some RNAs have been shown to allow their association to paraspeckles via protein binding. However, Neat1 could also be involved in the targeting of RNAs through direct RNA-RNA interactions. Using a RNA pull-down procedure adapted to select only RNAs engaged in direct RNA-RNA interactions and followed by RNA-seq we showed that in a rat pituitary cell line, GH4C1 cells, 1791 RNAs were associated with paraspeckles by direct interaction with Neat1. Neat1 was actually found able to bind more than 30% of the total transcripts targeted by the paraspeckles, we have identified in this cell line in a previous study. Furthermore, given the biological processes in which direct RNAs targets of Neat1 were involved as determined by gene ontology analysis, it was proposed that Neat1 played a major role in paraspeckle functions such as circadian rhythms, mRNA processing, RNA splicing and regulation of cell cycle. Finally, we provided evidence that direct RNA targets of Neat1 were preferentially bound to the 5’ end of Neat1 demonstrating that they are located in the shell region of paraspeckles.


2018 ◽  
Vol 46 (16) ◽  
pp. 8574-8589 ◽  
Author(s):  
Sunantha Sethuraman ◽  
Merin Thomas ◽  
Lauren A Gay ◽  
Rolf Renne

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Chia-Yu Chung ◽  
Amit Berson ◽  
Jason R. Kennerdell ◽  
Ashley Sartoris ◽  
Travis Unger ◽  
...  

Open Biology ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. 180110 ◽  
Author(s):  
Kaustav Mukherjee ◽  
Bruce Futcher ◽  
Janet Leatherwood

The RNA-binding protein Mei2 is crucial for meiosis in Schizosaccharomyces pombe. In mei2 mutants, pre-meiotic S-phase is blocked, along with meiosis. Mei2 binds a long non-coding RNA (lncRNA) called meiRNA, which is a ‘sponge RNA’ for the meiotic inhibitor protein Mmi1. The interaction between Mei2, meiRNA and Mmi1 protein is essential for meiosis. But mei2 mutants have stronger and different phenotypes than meiRNA mutants, since mei2Δ arrests before pre-meiotic S, while the meiRNA mutant arrests after pre-meiotic S but before meiosis. This suggests Mei2 may bind additional RNAs. To identify novel RNA targets of Mei2, which might explain how Mei2 regulates pre-meiotic S, we used RNA immunoprecipitation and cross-linking immunoprecipitation. In addition to meiRNA, we found the mRNAs for mmi1 (which encodes Mmi1) and for the S-phase transcription factor rep2 . There were also three other RNAs of uncertain relevance. We suggest that at meiotic initiation, Mei2 may sequester rep2 mRNA to help allow pre-meiotic S, and then may bind both meiRNA and mmi1 mRNA to inactivate Mmi1 at two levels, the protein level (as previously known), and also the mRNA level, allowing meiosis. We call Mei2–meiRNA a ‘double sponge’ (i.e. binding both an mRNA and its encoded protein).


eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Lihua Wang ◽  
Pengcheng Bu ◽  
Yiwei Ai ◽  
Tara Srinivasan ◽  
Huanhuan Joyce Chen ◽  
...  

The roles of long non-coding RNAs (lncRNAs) in regulating cancer and stem cells are being increasingly appreciated. Its diverse mechanisms provide the regulatory network with a bigger repertoire to increase complexity. Here we report a novel LncRNA, Lnc34a, that is enriched in colon cancer stem cells (CCSCs) and initiates asymmetric division by directly targeting the microRNA miR-34a to cause its spatial imbalance. Lnc34a recruits Dnmt3a via PHB2 and HDAC1 to methylate and deacetylate the miR-34a promoter simultaneously, hence epigenetically silencing miR-34a expression independent of its upstream regulator, p53. Lnc34a levels affect CCSC self-renewal and colorectal cancer (CRC) growth in xenograft models. Lnc34a is upregulated in late-stage CRCs, contributing to epigenetic miR-34a silencing and CRC proliferation. The fact that lncRNA targets microRNA highlights the regulatory complexity of non-coding RNAs (ncRNAs), which occupy the bulk of the genome.


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