LIN28 Selectively Modulates a Subclass of Let-7 MicroRNAs

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2018 Jul 21

PMID 30029005

Citations 62

Authors

Dmytro Ustianenko

Hua-Sheng Chiu

Thomas Treiber

Sebastien M Weyn-Vanhentenryck

Nora Treiber

Gunter Meister

Pavel Sumazin

Chaolin Zhang

Affiliations

Soon will be listed here.

Abstract

LIN28 is a bipartite RNA-binding protein that post-transcriptionally inhibits the biogenesis of let-7 microRNAs to regulate development and influence disease states. However, the mechanisms of let-7 suppression remain poorly understood because LIN28 recognition depends on coordinated targeting by both the zinc knuckle domain (ZKD), which binds a GGAG-like element in the precursor, and the cold shock domain (CSD), whose binding sites have not been systematically characterized. By leveraging single-nucleotide-resolution mapping of LIN28 binding sites in vivo, we determined that the CSD recognizes a (U)GAU motif. This motif partitions the let-7 microRNAs into two subclasses, precursors with both CSD and ZKD binding sites (CSD) and precursors with ZKD but no CSD binding sites (CSD). LIN28 in vivo recognition-and subsequent 3' uridylation and degradation-of CSD precursors is more efficient, leading to their stronger suppression in LIN28-activated cells and cancers. Thus, CSD binding sites amplify the regulatory effects of LIN28.

Citing Articles

Developing novel Lin28 inhibitors by computer aided drug design.

Matias-Barrios V, Radaeva M, Rosellinny G, Jia Q, Xie N, Villanueva M Cell Death Discov. 2025; 11(1):5.

PMID: 39800739 PMC: 11725581. DOI: 10.1038/s41420-024-02281-z.

Asynchronous Transitions from Hepatoblastoma to Carcinoma in High-Risk Pediatric Tumors.

Yu X, Sarabia S, Urbicain M, Somvanshi S, Patel R, Tran T bioRxiv. 2025; .

PMID: 39763896 PMC: 11703271. DOI: 10.1101/2024.12.24.630261.

The Role of Plzf in Spermatogonial Stem Cell Maintenance and Differentiation: Mapping the Transcriptional Dynamics and Key Interactions.

Ghasemi N, Azizi H, Razavi-Amoli S, Skutella T Cells. 2024; 13(23).

PMID: 39682679 PMC: 11640652. DOI: 10.3390/cells13231930.

Role of Csdc2 in Regulating Secondary Hair Follicle Growth in Cashmere Goats.

Zhu H, Li Y, Xu H, Ma Y, Andersson G, Bongcam-Rudloff E Int J Mol Sci. 2024; 25(15).

PMID: 39125915 PMC: 11313070. DOI: 10.3390/ijms25158349.

Poised PABP-RNA hubs implement signal-dependent mRNA decay in development.

Modic M, Kuret K, Steinhauser S, Faraway R, van Genderen E, Ruiz de Los Mozos I Nat Struct Mol Biol. 2024; 31(9):1439-1447.

PMID: 39054355 PMC: 11402784. DOI: 10.1038/s41594-024-01363-x.

References

Subramanian A, Kuehn H, Gould J, Tamayo P, Mesirov J . GSEA-P: a desktop application for Gene Set Enrichment Analysis. Bioinformatics. 2007; 23(23):3251-3. DOI: 10.1093/bioinformatics/btm369. View

Stormo G . DNA binding sites: representation and discovery. Bioinformatics. 2000; 16(1):16-23. DOI: 10.1093/bioinformatics/16.1.16. View

Wilbert M, Huelga S, Kapeli K, Stark T, Liang T, Chen S . LIN28 binds messenger RNAs at GGAGA motifs and regulates splicing factor abundance. Mol Cell. 2012; 48(2):195-206. PMC: 3483422. DOI: 10.1016/j.molcel.2012.08.004. View

Nowak J, Hobor F, Downie Ruiz Velasco A, Choudhury N, Heikel G, Kerr A . Lin28a uses distinct mechanisms of binding to RNA and affects miRNA levels positively and negatively. RNA. 2016; 23(3):317-332. PMC: 5311490. DOI: 10.1261/rna.059196.116. View

Viswanathan S, Daley G, Gregory R . Selective blockade of microRNA processing by Lin28. Science. 2008; 320(5872):97-100. PMC: 3368499. DOI: 10.1126/science.1154040. View

Rybak A, Fuchs H, Smirnova L, Brandt C, Pohl E, Nitsch R . A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment. Nat Cell Biol. 2008; 10(8):987-93. DOI: 10.1038/ncb1759. View

Trabucchi M, Briata P, Garcia-Mayoral M, Haase A, Filipowicz W, Ramos A . The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs. Nature. 2009; 459(7249):1010-4. PMC: 2768332. DOI: 10.1038/nature08025. View

Johnson S, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A . RAS is regulated by the let-7 microRNA family. Cell. 2005; 120(5):635-47. DOI: 10.1016/j.cell.2005.01.014. View

Treiber T, Treiber N, Plessmann U, Harlander S, Daiss J, Eichner N . A Compendium of RNA-Binding Proteins that Regulate MicroRNA Biogenesis. Mol Cell. 2017; 66(2):270-284.e13. DOI: 10.1016/j.molcel.2017.03.014. View

10.

Lambert N, Robertson A, Jangi M, McGeary S, Sharp P, Burge C . RNA Bind-n-Seq: quantitative assessment of the sequence and structural binding specificity of RNA binding proteins. Mol Cell. 2014; 54(5):887-900. PMC: 4142047. DOI: 10.1016/j.molcel.2014.04.016. View

11.

Hutvagner G, McLachlan J, Pasquinelli A, Balint E, Tuschl T, Zamore P . A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science. 2001; 293(5531):834-8. DOI: 10.1126/science.1062961. View

12.

Wang L, Nam Y, Lee A, Yu C, Roth K, Chen C . LIN28 Zinc Knuckle Domain Is Required and Sufficient to Induce let-7 Oligouridylation. Cell Rep. 2017; 18(11):2664-2675. DOI: 10.1016/j.celrep.2017.02.044. View

13.

Lee Y, Dutta A . The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev. 2007; 21(9):1025-30. PMC: 1855228. DOI: 10.1101/gad.1540407. View

14.

Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J . The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003; 425(6956):415-9. DOI: 10.1038/nature01957. View

15.

Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, Tuschl T . Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell. 2004; 15(2):185-97. DOI: 10.1016/j.molcel.2004.07.007. View

16.

Choudhury N, Nowak J, Zuo J, Rappsilber J, Spoel S, Michlewski G . Trim25 Is an RNA-Specific Activator of Lin28a/TuT4-Mediated Uridylation. Cell Rep. 2014; 9(4):1265-72. PMC: 4542301. DOI: 10.1016/j.celrep.2014.10.017. View

17.

Piskounova E, Polytarchou C, Thornton J, LaPierre R, Pothoulakis C, Hagan J . Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct mechanisms. Cell. 2011; 147(5):1066-79. PMC: 3227872. DOI: 10.1016/j.cell.2011.10.039. View

18.

Grishok A, Pasquinelli A, Conte D, Li N, Parrish S, Ha I . Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell. 2001; 106(1):23-34. DOI: 10.1016/s0092-8674(01)00431-7. View

19.

Heo I, Joo C, Kim Y, Ha M, Yoon M, Cho J . TUT4 in concert with Lin28 suppresses microRNA biogenesis through pre-microRNA uridylation. Cell. 2009; 138(4):696-708. DOI: 10.1016/j.cell.2009.08.002. View

20.

Mayr C, Hemann M, Bartel D . Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science. 2007; 315(5818):1576-9. PMC: 2556962. DOI: 10.1126/science.1137999. View