A novel class of small RNAs bind to MILI protein in mouse testes
Abstract
Small RNAs bound to Argonaute proteins recognize partially or fully complementary nucleic acid targets in diverse gene-silencing processes. A subgroup of the Argonaute proteins--known as the 'Piwi family'--is required for germ- and stem-cell development in invertebrates, and two Piwi members--MILI and MIWI--are essential for spermatogenesis in mouse. Here we describe a new class of small RNAs that bind to MILI in mouse male germ cells, where they accumulate at the onset of meiosis. The sequences of the over 1,000 identified unique molecules share a strong preference for a 5' uridine, but otherwise cannot be readily classified into sequence families. Genomic mapping of these small RNAs reveals a limited number of clusters, suggesting that these RNAs are processed from long primary transcripts. The small RNAs are 26-31 nucleotides (nt) in length--clearly distinct from the 21-23 nt of microRNAs (miRNAs) or short interfering RNAs (siRNAs)--and we refer to them as 'Piwi-interacting RNAs' or piRNAs. Orthologous human chromosomal regions also give rise to small RNAs with the characteristics of piRNAs, but the cloned sequences are distinct. The identification of this new class of small RNAs provides an important starting point to determine the molecular function of Piwi proteins in mammalian spermatogenesis.
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Ago3 regulates PIWI-interacting RNAs (piRNAs), a large class of highly conserved small noncoding RNAs that are responsible for silencing transposons.
“Ago3 regulates PIWI-interacting RNAs, or piRNAs, a large class of highly conserved small noncoding RNAs that are responsible for silencing transposons33,34.”
From Tau promotes neurodegeneration through global chromatin relaxation (2014) · cites this paper as [33]
Cites
Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes
Siepel, A., Bejerano, G., Pedersen, J. S., Hinrichs, A. S., Hou, M., Rosenbloom, K., Clawson, H., Spieth, J., Hillier, L. W., Richards, S., et al. (2005) · Genome Research · doi:10.1101/gr.3715005 · Cited by 4,408 · see citing works
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The role of non-coding RNAs in oncology
Slack, F. J., & Chinnaiyan, A. M. (2019) · Cell · doi:10.1016/j.cell.2019.10.017 · Cited by 1,619 · see citing works
The Piwi-piRNA Pathway Provides an Adaptive Defense in the Transposon Arms Race
Aravin, A. A., Hannon, G. J., & Brennecke, J. (2007) · Science · doi:10.1126/science.1146484 · Cited by 1,096 · see citing works
Self-citationNon-coding RNAs as regulators of gene expression and epigenetics
Kaikkonen, M. U., Lam, M. T. Y., & Glass, C. K. (2011) · Cardiovascular Research · doi:10.1093/cvr/cvr097 · Cited by 764 · see citing works
Tau promotes neurodegeneration through global chromatin relaxation
Frost, B., Hemberg, M., Lewis, J., & Feany, M. B. (2014) · Nature Neuroscience · doi:10.1038/nn.3639 · Cited by 519 · see citing works
“Ago3 regulates PIWI-interacting RNAs, or piRNAs, a large class of highly conserved small noncoding RNAs that are responsible for silencing transposons 33,34 .”
Juliano, C., Wang, J., & Lin, H. (2011) · Annual Review of Genetics · doi:10.1146/annurev-genet-110410-132541 · Cited by 374 · see citing works
Czech, B., Preall, J. B., McGinn, J., & Hannon, G. J. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.04.007 · Cited by 269 · see citing works
Modifiers of epigenetic reprogramming show paternal effects in the mouse
Chong, S., Vickaryous, N., Ashe, A., Zamudio, N., Youngson, N., Hemley, S., Stopka, T., Skoultchi, A., Matthews, J., Scott, H. S., et al. (2007) · Nature Genetics · doi:10.1038/ng2031 · Cited by 166 · see citing works
Connecting the dots between tau dysfunction and neurodegeneration
Frost, B., Götz, J., & Feany, M. B. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.07.005 · Cited by 124 · see citing works
Transcriptome-wide piRNA profiling in human brains of Alzheimer's disease
Qiu, W., Guo, X., Lin, X., Yang, Q., Zhang, W., Zhang, Y., Zuo, L., Zhu, Y., Li, C.-S. R., Ma, C., et al. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.05.020 · Cited by 105 · see citing works
Buiting, K., Nazlican, H., Galetzka, D., Wawrzik, M., Groβ, S., & Horsthemke, B. (2007) · Genomics · doi:10.1016/j.ygeno.2006.12.008 · Cited by 61 · see citing works
Larriba, E., & Del Mazo, J. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17040452 · Cited by 47 · see citing works
Correction: Germline Stem Cell Gene PIWIL2 Mediates DNA Repair through Relaxation of Chromatin
Yin, D.-T., Wang, Q., Chen, L., Liu, M.-Y., Han, C., Yan, Q., Shen, R., He, G., Duan, W., Li, J.-J., et al. (2011) · PLoS ONE · doi:10.1371/annotation/2c1c26ac-ee7e-417d-9852-4d2995ad102b · Cited by 19 · see citing works
RG motifs promote piRNA-mediated gene silencing in <i>C. elegans</i>
Wallis, D. C., & Phillips, C. M. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf1331 · Cited by 3 · see citing works
- Authors
- Aravin, A., Gaidatzis, D., Pfeffer, S., Lagos-Quintana, M., Landgraf, P., Iovino, N., Morris, P., Brownstein, M. J., Kuramochi-Miyagawa, S., Nakano, T., Chien, M., Russo, J. J., Ju, J., Sheridan, R., Sander, C., Zavolan, M., & Tuschl, T.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of Basel (CH)
- Centre National de la Recherche Scientifique (FR)
- Population Council (US)
- J. Craig Venter Institute (US)
- The University of Osaka (JP)
- Columbia University (US)
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Zavolan, Mihaela
- Tuschl, Thomas
- ORCID
- Venue
- Nature
- Published
- 2006-06-04
- Volume
- 442
- Issue
- 7099
- Pages
- 203-207
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2035930185
- Cited by
- 1,516
- References
- 1
- Citations by year
- 2026: 41 · 2025: 73 · 2024: 64 · 2023: 70 · 2022: 72 · 2021: 99 · 2020: 67 · 2019: 69 · 2018: 76 · 2017: 79 · 2016: 63 · 2015: 78 · 2014: 72 · 2013: 83 · 2012: 75
- FWCI
- 99.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- HAL (submittedVersion)
- Funders
- FRAXA Research Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD039024)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- piRNA, MILI, PIWI proteins, Argonaute proteins, RNA-induced silencing complex, small RNA, spermatogenesis, male germ cells, meiosis, mouse testis, human orthologs
- MeSH terms
- Animals, Animals, Newborn, Multigene Family, Humans, Male, Mice, Inbred C57BL, Proteins, RNA, Spermatogenesis, Testis, Time Factors, Mice, Argonaute Proteins
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