Extracellular microRNA 3’ end modification across diverse body fluids
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 iso...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-09-01
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| Series: | Epigenetics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15592294.2020.1834922 |
| _version_ | 1797678877959520256 |
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| author | Kikuye Koyano Jae Hoon Bahn Xinshu Xiao |
| author_facet | Kikuye Koyano Jae Hoon Bahn Xinshu Xiao |
| author_sort | Kikuye Koyano |
| collection | DOAJ |
| description | 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 hundreds of miRNAs with 3’ uridylation or adenylation, with the former being more prevalent. Among these miRNAs, up to 53% (22%) had an average 3’ uridylation (adenylation) level of at least 10% in a specific biofluid. 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 relatively robust 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. |
| first_indexed | 2024-03-11T23:06:19Z |
| format | Article |
| id | doaj.art-3cbf290ad0164d04befb7ba806e9cc90 |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:06:19Z |
| publishDate | 2021-09-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-3cbf290ad0164d04befb7ba806e9cc902023-09-21T13:09:24ZengTaylor & Francis GroupEpigenetics1559-22941559-23082021-09-011691000101510.1080/15592294.2020.18349221834922Extracellular microRNA 3’ end modification across diverse body fluidsKikuye Koyano0Jae Hoon Bahn1Xinshu Xiao2UCLAUCLAUCLAmicroRNAs (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 hundreds of miRNAs with 3’ uridylation or adenylation, with the former being more prevalent. Among these miRNAs, up to 53% (22%) had an average 3’ uridylation (adenylation) level of at least 10% in a specific biofluid. 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 relatively robust 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.http://dx.doi.org/10.1080/15592294.2020.1834922micrornanon-templated additionsextracellular rnacomputational analysisbiofluids |
| spellingShingle | Kikuye Koyano Jae Hoon Bahn Xinshu Xiao Extracellular microRNA 3’ end modification across diverse body fluids Epigenetics microrna non-templated additions extracellular rna computational analysis biofluids |
| title | Extracellular microRNA 3’ end modification across diverse body fluids |
| title_full | Extracellular microRNA 3’ end modification across diverse body fluids |
| title_fullStr | Extracellular microRNA 3’ end modification across diverse body fluids |
| title_full_unstemmed | Extracellular microRNA 3’ end modification across diverse body fluids |
| title_short | Extracellular microRNA 3’ end modification across diverse body fluids |
| title_sort | extracellular microrna 3 end modification across diverse body fluids |
| topic | microrna non-templated additions extracellular rna computational analysis biofluids |
| url | http://dx.doi.org/10.1080/15592294.2020.1834922 |
| work_keys_str_mv | AT kikuyekoyano extracellularmicrorna3endmodificationacrossdiversebodyfluids AT jaehoonbahn extracellularmicrorna3endmodificationacrossdiversebodyfluids AT xinshuxiao extracellularmicrorna3endmodificationacrossdiversebodyfluids |