Structural basis of microRNA length variety

Staręga-Rosłan, Julia; Król, Jacek; Kościańska, Edyta; Kozlowski, Piotr; Szlachcic, Wojciech J.; Sobczak, Krzysztof; Krzyżosiak, Włodzimierz J.

doi:10.1093/nar/gkq727

Cited by 164 publications

(171 citation statements)

References 33 publications

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“…S3). Previous Northern blotting experiments for miR-21 in RNA obtained from MCF7, HeLa, and HT29 cells (14) confirm the existence of both a 22-nt and a 23-nt mature miRNA in these cells.…”

Section: Significancementioning

confidence: 59%

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PAPD5-mediated 3′ adenylation and subsequent degradation of miR-21 is disrupted in proliferative disease

Boele

Persson

Shin

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

138

143

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Next-generation sequencing experiments have shown that microRNAs (miRNAs) are expressed in many different isoforms (isomiRs), whose biological relevance is often unclear. We found that mature miR-21, the most widely researched miRNA because of its importance in human disease, is produced in two prevalent isomiR forms that differ by 1 nt at their 3′ end, and moreover that the 3′ end of miR-21 is posttranscriptionally adenylated by the noncanonical poly(A) polymerase PAPD5. PAPD5 knockdown caused an increase in the miR-21 expression level, suggesting that PAPD5-mediated adenylation of miR-21 leads to its degradation. Exoribonuclease knockdown experiments followed by small-RNA sequencing suggested that PARN degrades miR-21 in the 3′-to-5′ direction. In accordance with this model, microarray expression profiling demonstrated that PAPD5 knockdown results in a down-regulation of miR-21 target mRNAs. We found that disruption of the miR-21 adenylation and degradation pathway is a general feature in tumors across a wide range of tissues, as evidenced by data from The Cancer Genome Atlas, as well as in the noncancerous proliferative disease psoriasis. We conclude that PAPD5 and PARN mediate degradation of oncogenic miRNA miR-21 through a tailing and trimming process, and that this pathway is disrupted in cancer and other proliferative diseases.nucleotidyl transferase | microRNA processing

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“…S3). Previous Northern blotting experiments for miR-21 in RNA obtained from MCF7, HeLa, and HT29 cells (14) confirm the existence of both a 22-nt and a 23-nt mature miRNA in these cells.…”

Section: Significancementioning

confidence: 59%

“…IsomiRs may be produced by differential excision by DICER1, which can lead to variations in the 5′ and 3′ ends of the mature miRNA (14). This can alter their affinity for Argonaute proteins (15) and also, in case of 5′ end variations, their target specificity (16).…”

Section: Significancementioning

confidence: 99%

PAPD5-mediated 3′ adenylation and subsequent degradation of miR-21 is disrupted in proliferative disease

Boele

Persson

Shin

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

138

143

View full text Add to dashboard Cite

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“…S1). 29,30,34 The bulge was found specifically in the 3 0 overhang of miR394*. However, miR394* is 21-nt long rather than the 22-nt reported previously.…”

Section: -Nt Mirna Duplexes Contain An Atypical Duplex Region or Ovmentioning

confidence: 82%

“…32 One miRNA precursor can produce isoforms of various lengths yet the dominant length varies even for miRNA within the same family. 30,33,34 For instance, A. thaliana MIR168a predominantly produces mature miRNA of 21 nt while MIR168b produces 21-nt and 22-nt miRNA species at comparable levels. 35 Asymmetric bulges have been shown to be responsible for the production of longer miRNAs in plants and animals as the unpaired bases within bulges are not measured by DCR or DCL proteins.…”

Section: Introductionmentioning

confidence: 99%

“…35 Asymmetric bulges have been shown to be responsible for the production of longer miRNAs in plants and animals as the unpaired bases within bulges are not measured by DCR or DCL proteins. 29,30,34,36 In A. thaliana, both 21-nt and 22-nt miRNAs associated with AGO1 are able to guide cleavage on their targets while 22-nt miRNAs are highly enriched among triggers that initiate the biogenesis of secondary small interfering RNAs (siRNAs) from their targets. 29,30 Besides 22 nt, 20 nt is a non-canonical miRNA length commonly observed in many plant species.…”

Section: Introductionmentioning

confidence: 99%

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Asymmetric bulges and mismatches determine 20-nt microRNA formation in plants

Lee

et al. 2015

RNA Biology

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Plant microRNAs (miRNAs) are predominantly 21 nucleotides (nt) long but non-canonical lengths of 22 and 20 nt are commonly observed in diverse plant species. While miRNAs longer than 21 nt can be attributed to the neglect of unpaired bases within asymmetric bulges by the ruler function of DICER-LIKE 1 (DCL1), how 20-nt miRNA is generated remains obscure. Analysis of small RNA data revealed that 20-nt miRNA can be divided into 3 main groups featured by atypical 3 0 overhangs or shorter duplex regions. Asymmetric bulges or mismatches at specific positions are commonly observed within each group and were shown to be crucial for 20-nt miRNA formation. Analysis of DCL1 cleavage sites on 20-nt miRNA precursors suggests that these determinants might alter precursor structure or trigger 3 0 -end decay of mature miRNA. The results herein advance our understanding of miRNA biogenesis and demonstrate that the effect of asymmetric bulges on miRNA length could be position-dependent.

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