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Quantitative single-cell splicing analysis reveals an ‘economy of scale’ filter for gene expression

Ding, Fangyuan and Elowitz, Michael B. (2018) Quantitative single-cell splicing analysis reveals an ‘economy of scale’ filter for gene expression. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20200601-094106134

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Abstract

In eukaryotic cells, splicing affects the fate of each pre-mRNA transcript, helping to determine whether it is ultimately processed into an mRNA, or degraded. The efficiency of splicing plays a key role in gene expression. However, because it depends on the levels of multiple isoforms at the same transcriptional active site (TAS) in the same cell, splicing efficiency has been challenging to measure. Here, we introduce a quantitative single-molecule FISH-based method that enables determination of the absolute abundances of distinct RNA isoforms at individual TASs. Using this method, we discovered that splicing efficiency behaves in an unexpected ‘economy of scale’ manner, increasing, rather than decreasing, with gene expression levels, opposite to a standard enzymatic process. This behavior could result from an observed correlation between splicing efficiency and spatial proximity to nuclear speckles. Economy of scale splicing represents a non-linear filter that amplifies the expression of genes when they are more strongly transcribed. This method will help to reveal the roles of splicing in the quantitative control of gene expression.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/457432DOIDiscussion Paper
ORCID:
AuthorORCID
Ding, Fangyuan0000-0003-0118-5441
Elowitz, Michael B.0000-0002-1221-0967
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Posted October 30, 2018. The work was funded by a Fellowship from the Schlumberger Foundation, by the Gordon and Betty Moore Foundation through Grant GBMF2809 to the Caltech Programmable Molecular Technology Initiative and the Institute for Collaborative Biotechnologies through grant W911NF-09-0001 from the U.S. Army Research Office. The content of the information does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred. M.B.E. is a Howard Hughes Medical Institute Investigator.
Funders:
Funding AgencyGrant Number
Schlumberger FoundationUNSPECIFIED
Gordon and Betty Moore FoundationGBMF2809
Army Research Office (ARO)W911NF-09-0001
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Record Number:CaltechAUTHORS:20200601-094106134
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200601-094106134
Official Citation:Quantitative single-cell splicing analysis reveals an ‘economy of scale’ filter for gene expression. Fangyuan Ding, Michael B. Elowitz. bioRxiv 457432; doi: https://doi.org/10.1101/457432
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103580
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:01 Jun 2020 16:45
Last Modified:10 Dec 2020 19:32

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