IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-63015-y.html
   My bibliography  Save this article

ERH promotes primary microRNA processing beyond cluster assistance

Author

Listed:
  • Harim Jang

    (Institute for Basic Science
    Seoul National University)

  • Junyoung Park

    (Institute for Basic Science
    Seoul National University)

  • V. Narry Kim

    (Institute for Basic Science
    Seoul National University)

Abstract

MicroRNA (miRNA) maturation is initiated by the Microprocessor complex, comprising DROSHA and DGCR8, that processes primary miRNAs (pri-miRNAs). Recent studies have identified ERH and SAFB2 as auxiliary factors that enhance the functionality of the Microprocessor. These factors are required for cluster assistance, where optimal pri-miRNAs facilitate the processing of adjacent suboptimal pri-miRNAs. However, the specific action mechanisms of ERH and SAFB2 have not yet been defined. In this study, we found that ERH broadly enhances the processing of pri-miRNAs regardless of their genomic contexts, affecting both stand-alone and clustered ones. Suboptimal hairpins are affected more prominently by ERH knockdown than efficiently processed hairpins. In contrast, SAFB2 specifically supports the processing of suboptimal pri-miRNA hairpins within clusters. This study reveals the distinct roles of ERH and SAFB2 in cluster assistance and presents a new model, in which SAFB2 facilitates the Microprocessor’s transfer between hairpins, while ERH enables the efficient processing of suboptimal pri-miRNAs.

Suggested Citation

  • Harim Jang & Junyoung Park & V. Narry Kim, 2025. "ERH promotes primary microRNA processing beyond cluster assistance," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63015-y
    DOI: 10.1038/s41467-025-63015-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-63015-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-63015-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Richard I. Gregory & Kai-ping Yan & Govindasamy Amuthan & Thimmaiah Chendrimada & Behzad Doratotaj & Neil Cooch & Ramin Shiekhattar, 2004. "The Microprocessor complex mediates the genesis of microRNAs," Nature, Nature, vol. 432(7014), pages 235-240, November.
    2. Ahmet M. Denli & Bastiaan B. J. Tops & Ronald H. A. Plasterk & René F. Ketting & Gregory J. Hannon, 2004. "Processing of primary microRNAs by the Microprocessor complex," Nature, Nature, vol. 432(7014), pages 231-235, November.
    3. Yoontae Lee & Chiyoung Ahn & Jinju Han & Hyounjeong Choi & Jaekwang Kim & Jeongbin Yim & Junho Lee & Patrick Provost & Olof Rådmark & Sunyoung Kim & V. Narry Kim, 2003. "The nuclear RNase III Drosha initiates microRNA processing," Nature, Nature, vol. 425(6956), pages 415-419, September.
    4. Shaohua Li & Trung Duc Nguyen & Thuy Linh Nguyen & Tuan Anh Nguyen, 2020. "Mismatched and wobble base pairs govern primary microRNA processing by human Microprocessor," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    5. Liping Deng & Ruotong Ren & Zunpeng Liu & Moshi Song & Jingyi Li & Zeming Wu & Xiaoqing Ren & Lina Fu & Wei Li & Weiqi Zhang & Pedro Guillen & Juan Carlos Izpisua Belmonte & Piu Chan & Jing Qu & Guang, 2019. "Stabilizing heterochromatin by DGCR8 alleviates senescence and osteoarthritis," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    6. Emily Bernstein & Amy A. Caudy & Scott M. Hammond & Gregory J. Hannon, 2001. "Role for a bidentate ribonuclease in the initiation step of RNA interference," Nature, Nature, vol. 409(6818), pages 363-366, January.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Thiago L. Knittel & Brooke E. Montgomery & Kailee J. Reed & Madeleine C. Chong & Ida J. Isolehto & Erin R. Cafferty & Margaret J. Smith & Reese A. Sprister & Colin N. Magelky & Hataichanok Scherman & , 2025. "Interdependence of Pasha and Drosha for localization and function of the Microprocessor in C. elegans," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    2. Bin Liu & Longyun Fang & Fule Liu & Xiaolong Wang & Junjie Chen & Kuo-Chen Chou, 2015. "Identification of Real MicroRNA Precursors with a Pseudo Structure Status Composition Approach," PLOS ONE, Public Library of Science, vol. 10(3), pages 1-20, March.
    3. Matvei Khoroshkin & Andrey Buyan & Martin Dodel & Albertas Navickas & Johnny Yu & Fathima Trejo & Anthony Doty & Rithvik Baratam & Shaopu Zhou & Sean B. Lee & Tanvi Joshi & Kristle Garcia & Benedict C, 2024. "Systematic identification of post-transcriptional regulatory modules," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    4. Jun Wang & Jinyong Huang & Yunlong Hu & Qianwen Guo & Shasha Zhang & Jinglin Tian & Yanqin Niu & Ling Ji & Yuzhong Xu & Peijun Tang & Yaqin He & Yuna Wang & Shuya Zhang & Hao Yang & Kang Kang & Xinchu, 2024. "Terminal modifications independent cell-free RNA sequencing enables sensitive early cancer detection and classification," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    5. Xiaorong Yang & Yanan Guo & Yane Du & Jinmei Yang & Shichao Li & Shengnan Liu & Ke Li & Dechun Zhang, 2014. "Serum MicroRNA-21 as a Diagnostic Marker for Lung Carcinoma: A Systematic Review and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 9(5), pages 1-7, May.
    6. Bidur Paudel & Si-Yeon Jeong & Carolina Pena Martinez & Alexis Rickman & Ashley Haluck-Kangas & Elizabeth T. Bartom & Kristina Fredriksen & Amira Affaneh & John A. Kessler & Joseph R. Mazzulli & Andre, 2024. "Death Induced by Survival gene Elimination (DISE) correlates with neurotoxicity in Alzheimer’s disease and aging," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    7. Katerina Gkirtzou & Ioannis Tsamardinos & Panagiotis Tsakalides & Panayiota Poirazi, 2010. "MatureBayes: A Probabilistic Algorithm for Identifying the Mature miRNA within Novel Precursors," PLOS ONE, Public Library of Science, vol. 5(8), pages 1-14, August.
    8. repec:plo:pone00:0054215 is not listed on IDEAS
    9. Le Thi Truc Linh, 2018. "The Microrna 29 family and its regulation," HO CHI MINH CITY OPEN UNIVERSITY JOURNAL OF SCIENCE - ENGINEERING AND TECHNOLOGY, HO CHI MINH CITY OPEN UNIVERSITY JOURNAL OF SCIENCE, HO CHI MINH CITY OPEN UNIVERSITY, vol. 8(1), pages 18-27.
    10. Trung Duc Nguyen & Tam Anh Trinh & Sheng Bao & Tuan Anh Nguyen, 2022. "Secondary structure RNA elements control the cleavage activity of DICER," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    11. Hengdong Zhang & Ming Xu & Qiuni Zhao & Kai Sun & Wei Gong & Qiaoyun Zhang & Baoli Zhu & Yan An, 2016. "Association between Polymorphism of Exportin-5 and Susceptibility to Lead Poisoning in a Chinese Population," IJERPH, MDPI, vol. 14(1), pages 1-8, December.
    12. Ying Wang & Xiushan Zheng & Zhiyong Zhang & Jinfeng Zhou & Guohong Zhao & Jianjun Yang & Limin Xia & Rui Wang & Xiqiang Cai & Hao Hu & Cailin Zhu & Yongzhan Nie & Kaichun Wu & Dexin Zhang & Daiming Fa, 2012. "MicroRNA-149 Inhibits Proliferation and Cell Cycle Progression through the Targeting of ZBTB2 in Human Gastric Cancer," PLOS ONE, Public Library of Science, vol. 7(10), pages 1-10, October.
    13. Sofia Khan & Dario Greco & Kyriaki Michailidou & Roger L Milne & Taru A Muranen & Tuomas Heikkinen & Kirsimari Aaltonen & Joe Dennis & Manjeet K Bolla & Jianjun Liu & Per Hall & Astrid Irwanto & Keith, 2014. "MicroRNA Related Polymorphisms and Breast Cancer Risk," PLOS ONE, Public Library of Science, vol. 9(11), pages 1-11, November.
    14. Marta Garcia-Montojo & Saeed Fathi & Cyrus Rastegar & Elena Rita Simula & Tara Doucet-O’Hare & Y. H. Hank Cheng & Rachel P. M. Abrams & Nicholas Pasternack & Nasir Malik & Muzna Bachani & Brianna Disa, 2024. "TDP-43 proteinopathy in ALS is triggered by loss of ASRGL1 and associated with HML-2 expression," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    15. Guangwen Long & Feng Wang & Quanlu Duan & Shenglan Yang & Fuqiong Chen & Wei Gong & Xu Yang & Yan Wang & Chen Chen & Dao Wen Wang, 2012. "Circulating miR-30a, miR-195 and let-7b Associated with Acute Myocardial Infarction," PLOS ONE, Public Library of Science, vol. 7(12), pages 1-8, December.
    16. San-Nung Chen & Renin Chang & Li-Te Lin & Chyi-Uei Chern & Hsiao-Wen Tsai & Zhi-Hong Wen & Yi-Han Li & Chia-Jung Li & Kuan-Hao Tsui, 2019. "MicroRNA in Ovarian Cancer: Biology, Pathogenesis, and Therapeutic Opportunities," IJERPH, MDPI, vol. 16(9), pages 1-14, April.
    17. Shuangmei Tian & Ziyu Zhao & Beibei Ren & Degeng Wang, 2024. "Non-Linear Relationship between MiRNA Regulatory Activity and Binding Site Counts on Target mRNAs," Data, MDPI, vol. 9(10), pages 1-13, September.
    18. repec:plo:pone00:0100055 is not listed on IDEAS
    19. Paola Mozzoni & Diana Poli & Silvana Pinelli & Sara Tagliaferri & Massimo Corradi & Delia Cavallo & Cinzia Lucia Ursini & Daniela Pigini, 2023. "Benzene Exposure and MicroRNAs Expression: In Vitro, In Vivo and Human Findings," IJERPH, MDPI, vol. 20(3), pages 1-16, January.
    20. Maurizio Marrale & Nadia Ninfa Albanese & Francesco Calì & Valentino Romano, 2014. "Assessing the Impact of Copy Number Variants on miRNA Genes in Autism by Monte Carlo Simulation," PLOS ONE, Public Library of Science, vol. 9(3), pages 1-10, March.
    21. Xiaoying Chen & Kosuke Yamaguchi & Brianna Rodgers & Delphine Goehrig & David Vindrieux & Xavier Lahaye & Matthieu Nolot & Laure Ferry & Sophie Lanciano & Nadine Martin & Pierre Dubus & Fumihito Miura, 2025. "DNA methylation protects cancer cells against senescence," Nature Communications, Nature, vol. 16(1), pages 1-22, December.
    22. Lingzi Xia & Yangwu Ren & Xue Fang & Zhihua Yin & Xuelian Li & Wei Wu & Peng Guan & Baosen Zhou, 2014. "Prognostic Role of Common MicroRNA Polymorphisms in Cancers: Evidence from a Meta-Analysis," PLOS ONE, Public Library of Science, vol. 9(10), pages 1-8, October.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63015-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.