@article{47f6e34c46aa42c6a25f30e862224e27,
title = "Kinetic modeling reveals additional regulation at co-transcriptional level by post-transcriptional sRNA regulators",
abstract = "Small RNAs (sRNAs) are important gene regulators in bacteria. Many sRNAs act post-transcriptionally by affecting translation and degradation of the target mRNAs upon base-pairing interactions. Here we present a general approach combining imaging and mathematical modeling to determine kinetic parameters at different levels of sRNA-mediated gene regulation that contribute to overall regulation efficacy. Our data reveal that certain sRNAs previously characterized as post-transcriptional regulators can regulate some targets co-transcriptionally, leading to a revised model that sRNA-mediated regulation can occur early in an mRNA's lifetime, as soon as the sRNA binding site is transcribed. This co-transcriptional regulation is likely mediated by Rho-dependent termination when transcription-coupled translation is reduced upon sRNA binding. Our data also reveal several important kinetic steps that contribute to the differential regulation of mRNA targets by an sRNA. Particularly, binding of sRNA to the target mRNA may dictate the regulation hierarchy observed within an sRNA regulon.",
keywords = "bacterial small RNA, fluorescence microscopy, gene regulation, mathematical modeling",
author = "Reyer, {Matthew A.} and Shriram Chennakesavalu and Heideman, {Emily M.} and Xiangqian Ma and Magda Bujnowska and Lu Hong and Dinner, {Aaron R.} and Vanderpool, {Carin K.} and Jingyi Fei",
note = "Funding Information: This work was supported by the NIH (R01 GM092830). J.F. also acknowledges the support from the Searle Scholars Program and an NIH Director's New Innovator Award (1DP2GM128185-01). A.R.D. acknowledges support from NSF (MCB-1953402). We thank Dr. M.S. Azam for useful discussion, MRSEC Shared User Facilities at the University of Chicago for 3D-printing service (NSF DMR-1420709 and DMR-2011854), and the Research Computing Center (RCC) at The University of Chicago for providing access to the Midway high-performance computing cluster. Conceptualization, M.A.R. C.K.V. and J.F.; methodology, M.A.R. and J.F.; investigation, M.A.R. E.M.H. X.M. and M.B.; modeling, M.A.R. S.C. and L.H; writing – original draft, M.A.R. and J.F.; writing – review & editing, M.A.R. A.R.D. C.K.V. and J.F.; funding acquisition, A.R.D. C.K.V. and J.F.; supervision, A.R.D. C.K.V. and J.F. The authors declare no competing interests. Funding Information: This work was supported by the NIH ( R01 GM092830 ). J.F. also acknowledges the support from the Searle Scholars Program and an NIH Director{\textquoteright}s New Innovator Award ( 1DP2GM128185-01 ). A.R.D. acknowledges support from NSF ( MCB-1953402 ). We thank Dr. M.S. Azam for useful discussion, MRSEC Shared User Facilities at the University of Chicago for 3D-printing service ( NSF DMR-1420709 and DMR-2011854 ), and the Research Computing Center (RCC) at The University of Chicago for providing access to the Midway high-performance computing cluster. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = sep,
day = "28",
doi = "10.1016/j.celrep.2021.109764",
language = "English (US)",
volume = "36",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "13",
}