Recent studies have revealed multifaceted roles of long noncoding RNAs (lncRNAs) in gene regulation, accompanying an increased understanding of lncRNA processing, localization, interacting macromolecules and structural modules. Here, progress and recently developed technological advances for understanding lncRNA biogenesis, modes of action and cellular phenotypes are highlighted, and challenges and opportunities towards higher-resolution and in vivo studies in this field are discussed.
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References
Statello, L., Guo, C. J., Chen, L. L. & Huarte, M. Nat. Rev. Mol. Cell Biol. 22, 96–118 (2021).
Wang, Y. et al. Nat. Cell Biol. 20, 1145–1158 (2018).
Lagarde, J. et al. Nat. Commun. 7, 12339 (2016).
Guo, C. J. et al. Cell 181, 621–636 (2020).
Much, C. et al. RNA 28, 842–853 (2022).
Stark, R., Grzelak, M. & Hadfield, J. Nat. Rev. Genet. 20, 631–656 (2019).
Cabili, M. N. et al. Genome Biol. 16, 20 (2015).
Zuckerman, B., Ron, M., Mikl, M., Segal, E. & Ulitsky, I. Mol. Cell 79, 251–267 (2020).
Cerase, A. et al. Proc. Natl Acad. Sci. USA 111, 2235–2240 (2014).
Sunwoo, H., Wu, J. Y. & Lee, J. T. Proc. Natl Acad. Sci. USA 112, E4216–E4225 (2015).
West, J. A. et al. J. Cell Biol. 214, 817–830 (2016).
Xing, Y. H. et al. Cell 169, 664–678 (2017).
Wu, M. et al. Science 373, 547–555 (2021).
Elguindy, M. M. & Mendell, J. T. Nature 595, 303–308 (2021).
Markaki, Y. et al. Cell 184, 6174–6192 (2021).
Liu, J., Yang, L. Z. & Chen, L. L. Curr. Opin. Genet. Dev. 72, 128–137 (2022).
Smola, M. J., Calabrese, J. M. & Weeks, K. M. Biochemistry 54, 6867–6875 (2015).
Liu, F., Somarowthu, S. & Pyle, A. M. Nat. Chem. Biol. 13, 282–289 (2017).
Weidmann, C. A., Mustoe, A. M., Jariwala, P. B., Calabrese, J. M. & Weeks, K. M. Nat. Biotechnol. 39, 347–356 (2021).
Yang, M. et al. Nature https://doi.org/10.1038/s41586-022-05135-9 (2022).
Xiang, J. F. et al. Cell Res. 24, 513–531, https://doi.org/10.1038/cr.2014.35 (2014).
Gutschner, T. et al. Cancer Res. 73, 1180–1189 (2013).
Sauvageau, M. et al. eLife 2, e01749 (2013).
Zhu, S. et al. Nat. Biotechnol. 34, 1279–1286 (2016).
Cai, P. et al. Genome Res. 30, 22–34 (2020).
Joung, J. et al. Nature 548, 343–346 (2017).
Yin, Y. et al. Cell Stem Cell 16, 504–516 (2015).
Liu, S. J. et al. Science 355, aah7111 (2017).
Bester, A. C. et al. Cell 173, 649–664 (2018).
Zibitt, M. S., Hartford, C. C. R. & Lal, A. RNA Biol. 18, 2097–2106 (2021).
Liu, S. J. et al. Genome Biol. 21, 83 (2020).
Yao, R. W., Wang, Y. & Chen, L. L. Nat. Cell Biol. 21, 542–551 (2019).
Quinodoz, S. A. et al. Cell 184, 5775–5790 (2021).
Kappel, K. et al. Nat. Methods 17, 699–707 (2020).
Pickar-Oliver, A. & Gersbach, C. A. Nat. Rev. Mol. Cell Biol. 20, 490–507 (2019).
Yang, L. & Chen, J. Trends Biochem. Sci. 45, 874–888 (2020).
Acknowledgements
The author is grateful to L. Yang at Fudan University and G. Carmichael at UConn Health for reading the paper. This work is supported by the CAS Project for Young Scientists in Basic Research (YSBR-009), the Shanghai Municipal Commission for Science and Technology (20JC1410300), the National Natural Science Foundation of China (31821004, 31830108, 31725009 and 91940303) and the HHMI International Program (55008728). L.-L.C. acknowledges support from the Xplorer Prize.
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Chen, LL. Towards higher-resolution and in vivo understanding of lncRNA biogenesis and function. Nat Methods 19, 1152–1155 (2022). https://doi.org/10.1038/s41592-022-01626-9
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DOI: https://doi.org/10.1038/s41592-022-01626-9
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