In recent years, the number of annotated noncoding RNAs (ncRNAs) and RNA-binding proteins (RBPs) has increased dramatically. The wide range of RBPs identified highlights the enormous potential for RNA in virtually all aspects of cell biology, from transcriptional regulation to metabolic control. Yet, there is a growing gap between what is possible and what has been demonstrated to be functionally important. Here we highlight recent methodological developments in the study of RNA–protein interactions, discuss the challenges and opportunities for exploring their functional roles, and provide our perspectives on what is needed to bridge the gap in this rapidly expanding field.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Frankish, A. et al. Nucleic Acids Res. 49, D916–D923 (2021).
Rinn, J. L. & Chang, H. Y. Annu. Rev. Biochem. 81, 145–166 (2012).
Quinodoz, S. A. et al. Cell 184, 5775–5790 (2021).
Kaneko, S. et al. Mol. Cell 53, 290–300 (2014).
Tsai, M. C. et al. Science 329, 689–693 (2010).
Hansen, A. S. et al. Mol. Cell 76, 395–411 (2019).
Saldaña-Meyer, R. et al. Mol. Cell 76, 412–422 (2019).
Mumbach, M. R. et al. Nat. Methods 16, 489–492 (2019).
Zovoilis, A., Cifuentes-Rojas, C., Chu, H.-P., Hernandez, A. J. & Lee, J. T. Cell 167, 1788–1802 (2016).
Di Ruscio, A. et al. Nature 503, 371–376 (2013).
Lee, S. et al. Cell 164, 69–80 (2016).
Kaneko, S., Son, J., Shen, S. S., Reinberg, D. & Bonasio, R. Nat. Struct. Mol. Biol. 20, 1258–1264 (2013).
Beltran, M. et al. Genome Res. 26, 896–907 (2016).
Davidovich, C., Zheng, L., Goodrich, K. J. & Cech, T. R. Nat. Struct. Mol. Biol. 20, 1250–1257 (2013).
He, C. et al. Mol. Cell 64, 416–430 (2016).
Castello, A. et al. Mol. Cell 63, 696–710 (2016).
Bateman, A. et al. Nucleic Acids Res. 49, D480–D489 (2021).
Ule, J. et al. Science 302, 1212–1215 (2003).
Van Nostrand, E. L. et al. Nat. Methods 13, 508–514 (2016).
Zarnegar, B. J. et al. Nat. Methods 13, 489–492 (2016).
Heard, E. & Disteche, C. M. Genes Dev. 20, 1848–1867 (2006).
Brockdorff, N. et al. Nature 351, 329–331 (1991).
Chu, C. et al. Cell 161, 404–416 (2015).
McHugh, C. A. et al. Nature 521, 232–236 (2015).
Minajigi, A. et al. Science 349, aab2276 (2015).
Clemson, C. M., McNeil, J. A., Willard, H. F. & Lawrence, J. B. J. Cell Biol. 132, 259–275 (1996).
Penny, G. D., Kay, G. F., Sheardown, S. A., Rastan, S. & Brockdorff, N. Nature 379, 131–137 (1996).
Plath, K. et al. Science 300, 131–135 (2003).
Wutz, A., Rasmussen, T. P. & Jaenisch, R. Nat. Genet. 30, 167–174 (2002).
Zhao, J., Sun, B. K., Erwin, J. A., Song, J.-J. & Lee, J. T. Science 322, 750–756 (2008).
Margueron, R. & Reinberg, D. Nature 469, 343–349 (2011).
Kalantry, S. & Magnuson, T. PLoS Genet. 2, e66 (2006).
Schoeftner, S. et al. EMBO J. 25, 3110–3122 (2006).
Zhao, J. et al. Mol. Cell 40, 939–953 (2010).
Mili, S. & Steitz, J. A. RNA 10, 1692–1694 (2004).
Davidovich, C. et al. Mol. Cell 57, 552–558 (2015).
Rosenberg, M. et al. Nat. Struct. Mol. Biol. 28, 103–117 (2021).
Hafner, M. et al. Nat. Rev. Methods Primers 1, 20 (2021).
Dossin, F. et al. Nature 578, 455–460 (2020).
Chen, C.-K. et al. Science 354, 468–472 (2016).
Lu, Z. et al. Nat. Commun. 11, 6163 (2020).
Portoso, M. et al. EMBO J. 36, 981–994 (2017).
Rinn, J. L. et al. Cell 129, 1311–1323 (2007).
Jeon, Y. & Lee, J. T. Cell 146, 119–133 (2011).
Huppertz, I. et al. Mol. Cell 82, 2666–2680 (2022).
Guttman, M. et al. Nature 477, 295–300 (2011).
Wang, K. C. et al. Nature 472, 120–124 (2011).
Holmes, Z. E. et al. Nat. Commun. 11, 1805 (2020).
Porter, D. F. et al. Nat. Commun. 12, 1569 (2021).
Sharma, D. et al. Nature 591, 152–156 (2021).
Acknowledgements
The authors thank I.-M. Strazhnik for Fig. 1 and S. Hiley for editing. J.K.G. is supported by the University of Southern California MD/PhD program. Research in the Guttman laboratory is funded by the National Institutes of Health (NIH) 4DN program, an NIH Director’s Transformative R01 award, the Chan Zuckerberg Initiative and funds from California Institute of Technology.
Author information
Authors and Affiliations
Contributions
The authors contributed equally to all aspects of the article.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Rights and permissions
About this article
Cite this article
Guo, J.K., Guttman, M. Regulatory non-coding RNAs: everything is possible, but what is important?. Nat Methods 19, 1156–1159 (2022). https://doi.org/10.1038/s41592-022-01629-6
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41592-022-01629-6