3′ Uridylation Confers miRNAs with Non-canonical Target Repertoires

Yang, Acong; Ros, Xavier Bofill-De; Shao, Tiejuan; Jiang, Mier; Li, Katherine; Villanueva, Patricia; Dai, Li-Shang; Gu, Shuo

doi:10.1016/j.molcel.2019.05.014

Cited by 71 publications

(96 citation statements)

References 65 publications

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“…1B). In addition, a concomitant increase of 3' adenylation levels was observed, consistent with previous literature 20, 24 . These results confirm the validity of our pipeline in identifying biologically relevant NTAs.…”

Section: Minta: a Bioinformatic Pipeline To Identify Mirna Ntassupporting

confidence: 92%

Extracellular microRNA 3’ end modification across diverse body fluids

Koyano

Bahn

Xiao

2020

Preprint

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microRNAs (miRNAs) are small non-coding RNAs that play critical roles in gene regulation. The presence of miRNAs in extracellular biofluids is increasingly recognized. However, most previous characterization of extracellular miRNAs focused on their overall expression levels. Alternative sequence isoforms and modifications of miRNAs were rarely considered in the extracellular space. Here, we developed a highly accurate bioinformatic method, called miNTA, to identify 3' non-templated additions (NTAs) of miRNAs using small RNA-sequencing data. Using miNTA, we conducted an in-depth analysis of miRNA 3' NTA profiles in 1047 extracellular RNA-sequencing data sets of 4 types of biofluids. This analysis identified abundant 3' uridylation and adenylation of miRNAs, with an estimated false discovery rate of <5%. Strikingly, we found that 3' uridylation levels enabled segregation of different types of biofluids, more effectively than overall miRNA expression levels. This observation suggests that 3' NTA levels possess fluid-specific information insensitive to batch effects. In addition, we observed that extracellular miRNAs with 3' uridylations are enriched in processes related to angiogenesis, apoptosis and inflammatory response, and this type of modification may stabilize base-pairing between miRNAs and their target genes. Together, our study provides a comprehensive landscape of miRNA NTAs in human biofluids, which paves way for further biomarker discoveries. The insights generated in our work built a foundation for future functional, mechanistic and translational discoveries.

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Section: Minta: a Bioinformatic Pipeline To Identify Mirna Ntassupporting

confidence: 92%

Extracellular microRNA 3’ end modification across diverse body fluids

Koyano

Bahn

Xiao

2020

Preprint

View full text Add to dashboard Cite

show abstract

“…By the way, in a subset of sites, the 3′ end pairing can make help for target recognition, particularly nucleotides 13-16 (the supplementary region) [43]. Recent findings have also shown that 3′ end pairing on uridylated miRNAs can also contribute to novel target recognition [44].…”

Section: Effects Of Mirnamentioning

confidence: 99%

miRNA-based biomarkers, therapies, and resistance in Cancer

et al. 2020

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MicroRNAs (miRNAs), small non-coding RNAs (ncRNAs) of about 22 nucleotides in size, play important roles in gene regulation, and their dysregulation is implicated in human diseases including cancer. A variety of miRNAs could take roles in the cancer progression, participate in the process of tumor immune, and function with miRNA sponges. During the last two decades, the connection between miRNAs and various cancers has been widely researched. Based on evidence about miRNA, numerous potential cancer biomarkers for the diagnosis and prognosis have been put forward, providing a new perspective on cancer screening. Besides, there are several miRNA-based therapies among different cancers being conducted, advanced treatments such as the combination of synergistic strategies and the use of complementary miRNAs provide significant clinical benefits to cancer patients potentially. Furthermore, it is demonstrated that many miRNAs are engaged in the resistance of cancer therapies with their complex underlying regulatory mechanisms, whose comprehensive cognition can help clinicians and improve patient prognosis. With the belief that studies about miRNAs in human cancer would have great clinical implications, we attempt to summarize the current situation and potential development prospects in this review.

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“…Also, interestingly, certain elongated miR-27 isomiRs may acquire altered ability to repress target mRNAs depending on the mode of miRNA-target interaction (miRNA-like vs. siRNA-like). Moreover, it is becoming clear that miRNA tailing can alter the specificity of miRNA repression, as in the case of miR-27 uridylation, which can compensate for imperfect seed base-pairing and repress noncanonical targets (Yang et al 2019).…”

Section: Outstanding Questionsmentioning

confidence: 99%

How Complementary Targets Expose the microRNA 3′ End for Tailing and Trimming during Target-Directed microRNA Degradation

Pawlica

Sheu‐Gruttadauria

MacRae

et al. 2019

Cold Spring Harb Symp Quant Biol

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microRNAs (miRNAs) are crucial for posttranscriptional regulation of messenger RNAs. "Classical" miRNA targets predominantly interact with the miRNA seed sequence located near the miRNA 5 0 end. Interestingly, certain transcripts that exhibit extensive complementarity to the miRNAs 3 0 region, instead of being subjected to regulation, induce miRNA decay in a process termed target-directed miRNA degradation (TDMD). Here, we review recent advances in understanding the molecular mechanisms of TDMD. Specifically, we discuss how extensive miRNA complementarity to TDMD-inducing targets results in displacement of the miRNA 3 0 end from its protective pocket in the Argonaute protein. Unprotected miRNA 3 0 ends are then available for enzymatic attack by still-unidentified cellular enzymes. Identification of these cellular enzymes and discovery of additional TDMD-inducing transcripts are subjects for future research.

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3′ Uridylation Confers miRNAs with Non-canonical Target Repertoires

Cited by 71 publications

References 65 publications

Extracellular microRNA 3’ end modification across diverse body fluids

Extracellular microRNA 3’ end modification across diverse body fluids

miRNA-based biomarkers, therapies, and resistance in Cancer

How Complementary Targets Expose the microRNA 3′ End for Tailing and Trimming during Target-Directed microRNA Degradation

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