Uracils at nucleotide position 9–11 are required for the rapid turnover of miR-29 family
Open accessAbstract
MicroRNAs are endogenous small RNA molecules that regulate gene expression. Although the biogenesis of microRNAs and their regulation have been thoroughly elucidated, the degradation of microRNAs has not been fully understood. Here by using the pulse-chase approach, we performed the direct measurement of microRNA lifespan. Five representative microRNAs demonstrated a general feature of relatively long lifespan. However, the decay dynamic varies considerably between these individual microRNAs. Mutation analysis of miR-29b sequence revealed that uracils at nucleotide position 9-11 are required for its rapid decay, in that both specific nucleotides and their position are critical. The effect of uracil-rich element on miR-29b decay dynamic occurs in duplex but not in single strand RNA. Moreover, analysis of published data on microRNA expression profile during development reveals that a substantial subset of microRNAs with the uracil-rich sequence tends to be down-regulated compared to those without the sequence. Among them, Northern blotting shows that miR-29c and fruit fly bantam possess a relatively rapid turnover rate. The effect of uracil-rich sequence on microRNA turnover depends on the sequence context. The present work indicates that microRNAs contain sequence information in the middle region besides the sequence element at both ends.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
miR-29a is the most abundantly expressed and stable among the miR-29 family.
“miR-29a, which is the most abundantly expressed and stable among the family [43]”
From miRNA family miR-29 inhibits PINK1-PRKN signaling via ATG9A (2026) · cites this paper as [43]
The Results (Figure 3B and the section on rapid turnover) show that miR-29a is more stable than miR-29b and miR-29c in the authors’ HeLa-cell assay. The paper does not establish that miR-29a is the most abundantly expressed family member; its abundance measurements concern transfected miRNA mimickers rather than a comparison of endogenous family-member expression. No page numbers are available in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredmiR-29b and miR-29c share a tri-uracil element at nucleotide positions 9-11 that causes their rapid decay.
“miR-29b and miR-29c share a tri-uracil element at nucleotide positions 9–11 that causes their rapid decay [43].”
From miRNA family miR-29 inhibits PINK1-PRKN signaling via ATG9A (2026) · cites this paper as [43]
In Results (“Uracils at nucleotide position 9–11 of miR-29b are required for its rapid decay”; page unavailable), replacing those uracils stabilizes miR-29b, supporting their role in its rapid decay. Results (“A subset of miRNAs with uracils at nucleotide positions 9–11 possesses rapid turnover”; page unavailable) reports relatively rapid turnover for miR-29c, but does not establish that the element causes miR-29c’s decay. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A Mammalian microRNA Expression Atlas Based on Small RNA Library Sequencing
Landgraf, P., Rusu, M., Sheridan, R., Sewer, A., Iovino, N., Aravin, A., Pfeffer, S., Rice, A., Kamphorst, A. O., Landthaler, M., et al. (2007) · Cell · doi:10.1016/j.cell.2007.04.040 · Cited by 3,626 · see citing works
Flagged first, then by citations
Research works printed but not linked: 37
- [1]Cai X Hagedorn CH Cullen BR Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs RNA 2004 10 1957 1966 15525708 PMC1370684
- [2]Lee Y Kim M Han J Yeom KH Lee S Baek SH Kim VN MicroRNA genes are transcribed by RNA polymerase II EMBO J. 2004 23 4051 4060 15372072 PMC524334
- [3]Borchert GM Lanier W Davidson BL RNA polymerase III transcribes human microRNAs Nat. Struct. Mol. Biol. 2006 13 1097 1101 17099701
- [4]Lee Y Ahn C Han J Choi H Kim J Yim J Lee J Provost P Radmark O Kim S The nuclear RNase III Drosha initiates microRNA processing Nature 2003 425 415 419 14508493
- [5]Denli AM Tops BB Plasterk RH Ketting RF Hannon GJ Processing of primary microRNAs by the Microprocessor complex Nature 2004 432 231 235 15531879
- [6]Grishok A Pasquinelli AE Conte D Li N Parrish S Ha I Baillie DL Fire A Ruvkun G Mello CC Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing Cell 2001 106 23 34 11461699
- [7]Hutvagner G McLachlan J Pasquinelli AE Balint E Tuschl T Zamore PD A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA Science 2001 293 834 838 11452083
- [8]Yi R Qin Y Macara IG Cullen BR Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs Genes Dev. 2003 17 3011 3016 14681208 PMC305252
- [9]Bohnsack MT Czaplinski K Gorlich D Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs RNA 2004 10 185 191 14730017 PMC1370530
- [10]Winter J Jung S Keller S Gregory RI Diederichs S Many roads to maturity: microRNA biogenesis pathways and their regulation Nat. Cell. Biol. 2009 11 228 234 19255566
- [11]Smalheiser NR Regulation of mammalian microRNA processing and function by cellular signaling and subcellular localization Biochim. Biophys. Acta 2008 1779 678 681 18433727 PMC2628772
- [12]van Rooij E Sutherland LB Qi X Richardson JA Hill J Olson EN Control of stress-dependent cardiac growth and gene expression by a microRNA Science 2007 316 575 579 17379774
- [13]Hwang HW Wentzel EA Mendell JT A hexanucleotide element directs microRNA nuclear import Science 2007 315 97 100 17204650
- [14]Rajasethupathy P Fiumara F Sheridan R Betel D Puthanveettil SV Russo JJ Sander C Tuschl T Kandel E Characterization of small RNAs in aplysia reveals a role for miR-124 in constraining synaptic plasticity through CREB Neuron 2009 63 803 817 19778509 PMC2875683
- [15]Sethi P Lukiw WJ Micro-RNA abundance and stability in human brain: specific alterations in Alzheimer's disease temporal lobe neocortex Neurosci. Lett. 2009 459 100 104 19406203
- [16]Krol J Busskamp V Markiewicz I Stadler MB Ribi S Richter J Duebel J Bicker S Fehling HJ Schubeler D Characterizing light-regulated retinal microRNAs reveals rapid turnover as a common property of neuronal microRNAs Cell 2010 141 618 631 20478254
- [17]Bail S Swerdel M Liu H Jiao X Goff LA Hart RP Kiledjian M Differential regulation of microRNA stability RNA 2010 16 1032 1039 20348442 PMC2856875
- [18]Diederichs S Haber DA Dual role for argonautes in microRNA processing and posttranscriptional regulation of microRNA expression Cell 2007 131 1097 1108 18083100
- [19]Yu Z Hecht NB The DNA/RNA-binding protein, translin, binds microRNA122a and increases its in vivo stability J. Androl. 2008 29 572 579 18567644
- [20]Ramachandran V Chen X Degradation of microRNAs by a family of exoribonucleases in Arabidopsis Science 2008 321 1490 1492 18787168 PMC2570778
- [21]Chatterjee S Grosshans H Active turnover modulates mature microRNA activity in Caenorhabditis elegans Nature 2009 461 546 549 19734881
- [22]Wilusz CJ Wilusz J New ways to meet your (3′) end oligouridylation as a step on the path to destruction Genes Dev. 2008 22 1 7 18172159 PMC2731568
- [23]Katoh T Sakaguchi Y Miyauchi K Suzuki T Kashiwabara S Baba T Suzuki T Selective stabilization of mammalian microRNAs by 3′ adenylation mediated by the cytoplasmic poly(A) polymerase GLD-2 Genes Dev. 2009 23 433 438 19240131 PMC2648654
- [24]Ross J mRNA stability in mammalian cells Microbiol. Rev. 1995 59 423 450 7565413 PMC239368
- [26]Park SY Lee JH Ha M Nam JW Kim VN miR-29 miRNAs activate p53 by targeting p85 alpha and CDC42 Nat. Struct. Mol. Biol. 2009 16 23 29 19079265
- [27]Hwang HW Wentzel EA Mendell JT Cell–cell contact globally activates microRNA biogenesis Proc. Natl Acad. Sci. USA 2009 106 7016 7021 19359480 PMC2678439
- [28]Czech B Zhou R Erlich Y Brennecke J Binari R Villalta C Gordon A Perrimon N Hannon GJ Hierarchical rules for Argonaute loading in Drosophila Mol. Cell 2009 36 445 456 19917252 PMC2795325
- [29]Okamura K Liu N Lai EC Distinct mechanisms for microRNA strand selection by Drosophila Argonautes Mol. Cell 2009 36 431 444 19917251 PMC2785079
- [30]Niwa R Slack FJ The evolution of animal microRNA function Curr. Opin. Genet Dev. 2007 17 145 150 17317150
- [31]Kato M de Lencastre A Pincus Z Slack FJ Dynamic expression of small non-coding RNAs, including novel microRNAs and piRNAs/21U-RNAs, during Caenorhabditis elegans development Genome Biol. 2009 10 R54 19460142 PMC2718520
- [32]Ruby JG Stark A Johnston WK Kellis M Bartel DP Lai EC Evolution, biogenesis, expression, and target predictions of a substantially expanded set of Drosophila microRNAs Genome Res. 2007 17 1850 1864 17989254 PMC2099593
- [33]Chen PY Manninga H Slanchev K Chien M Russo JJ Ju J Sheridan R John B Marks DS Gaidatzis D The developmental miRNA profiles of zebrafish as determined by small RNA cloning Genes Dev. 2005 19 1288 1293 15937218 PMC1142552
- [34]Brennecke J Hipfner DR Stark A Russell RB Cohen SM bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila Cell 2003 113 25 36 12679032
- [35]Wang Y Sheng G Juranek S Tuschl T Patel DJ Structure of the guide-strand-containing argonaute silencing complex Nature 2008 456 209 213 18754009 PMC4689319
- [36]Tang F Hajkova P O’Carroll D Lee C Tarakhovsky A Lao K Surani MA MicroRNAs are tightly associated with RNA-induced gene silencing complexes in vivo Biochem. Biophys. Res. Commun. 2008 372 24 29 18474225 PMC7612963
- [37]Yang E van Nimwegen E Zavolan M Rajewsky N Schroeder M Magnasco M Darnell JE Jr Decay rates of human mRNAs: correlation with functional characteristics and sequence attributes Genome Res. 2003 13 1863 1872 12902380 PMC403777
- [38]Tili E Michaille JJ Cimino A Costinean S Dumitru CD Adair B Fabbri M Alder H Liu CG Calin GA Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock J. Immunol. 2007 179 5082 5089 17911593
Cited by
Sorted by citations
miRNA family miR-29 inhibits PINK1-PRKN signaling via ATG9A
Markham, B. N., Ramnarine, C., Kim, S., Grever, W. E., Soto-Beasley, A. I., Heckman, M. G., Ren, Y., Osborne, A. C., Kehili, M., Bhagwate, A. V., et al. (2026) · Molecular Neurodegeneration Advances · doi:10.1186/s44477-026-00029-w
- Authors
- Zhang, Z., Zou, J., Wang, G.-K., Zhang, J.-T., Huang, S., Qin, Y.-W., & Jing, Q.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Qin, Yong-Wen
- Jing, Qing
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-02-01
- Volume
- 39
- Issue
- 10
- Pages
- 4387-4395
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC3105410
- OpenAlex
- W2137544017
- Cited by
- 50
- References
- 1
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2022: 4 · 2021: 5 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 4 · 2015: 5 · 2014: 6 · 2013: 3 · 2012: 7
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (30770457)
- Chinese Academy of Sciences (KSCX2-YW-R)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Keywords
- microRNA degradation, miR-29b, RNA duplex, sequence context, miR-29c, bantam microRNA, microRNA biogenesis
- MeSH terms
- HeLa Cells, Humans, RNA, Double-Stranded, Uracil, RNA Stability, MicroRNAs
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review