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The variables on RNA molecules: concert or cacophony? Answers in long-read sequencing

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Long-read sequencing has become a widely employed technology that enables a comprehensive view of RNA transcripts. Here, we discuss the importance of long-read sequencing in interpreting the variables along RNA molecules, such as polyadenylation sites, transcription start sites, splice sites and other RNA modifications. In addition, we highlight the history of short-read and long-read technologies and their advantages and disadvantages, as well as future directions in the field.

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Fig. 1: RNA variables and their non-random combinations.
Fig. 2: Long-read sequencing applications.
Fig. 3: An overview and timeline of various SRS and LRS technologies.

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Acknowledgements

H.U.T. is supported by NIGMS grant 1R01GM135247-01, Brain Initiative grant 1RF1MH121267-01, NIDA grant U01 DA053625-01 and the Feil Family Foundation. C.F. is supported by NSF GRFP No. NSF 2139291. N.B. is supported by NIDA T32 grant 5T32DA039080-0. S.P. is supported by NIGMS grant 1R01GM135247-03S1. Opinions, findings, conclusions or recommendations herein are those of the authors and do not necessarily reflect the views of NSF or NIH.

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Author notes

  1. These authors contributed equally: Careen Foord, Justine Hsu, Julien Jarroux.

Authors and Affiliations

  1. Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA

    Careen Foord, Justine Hsu, Julien Jarroux, Wen Hu, Natan Belchikov, Shaun Pollard, Yi He, Anoushka Joglekar & Hagen U. Tilgner

  2. Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA

    Careen Foord, Justine Hsu, Julien Jarroux, Wen Hu, Natan Belchikov, Shaun Pollard, Yi He, Anoushka Joglekar & Hagen U. Tilgner

  3. Physiology, Biophysics & Systems Biology Program, Weill Cornell Medicine, New York, NY, USA

    Natan Belchikov

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C.F., J.H., J.J. and H.U.T. wrote the manuscript. W.H., N.B., S.P., Y.I. and A.J. revised the manuscript.

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Correspondence to Hagen U. Tilgner.

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Foord, C., Hsu, J., Jarroux, J. et al. The variables on RNA molecules: concert or cacophony? Answers in long-read sequencing. Nat Methods 20, 20–24 (2023). https://doi.org/10.1038/s41592-022-01715-9

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