Dynamic features of gene expression control by small regulatory RNAs

TY - JOUR

T1 - Dynamic features of gene expression control by small regulatory RNAs

AU - Mitarai, Namiko

AU - Benjamin, Julie-Anna M

AU - Krishna, Sandeep

AU - Semsey, Szabolcs

AU - Csiszovszki, Zsolt

AU - Massé, Eric

AU - Sneppen, Kim

PY - 2009/6/30

Y1 - 2009/6/30

N2 - Small regulatory RNAs (sRNAs) in eukaryotes and bacteria play an important role in the regulation of gene expression either by binding to regulatory proteins or directly to target mRNAs. Two of the best-characterized bacterial sRNAs, Spot42 and RyhB, form a complementary pair with the ribosome binding region of their target mRNAs, thereby inhibiting translation or promoting mRNA degradation. To investigate the steady-state and dynamic potential of such sRNAs, we examine the 2 key parameters characterizing sRNA regulation: the capacity to overexpress the sRNA relative to its target mRNA and the speed at which the target mRNA is irreversibly inactivated. We demonstrate different methods to determine these 2 key parameters, for Spot42 and RyhB, which combine biochemical and genetic experiments with computational analysis. We have developed a mathematical model that describes the functional properties of sRNAs with various characteristic parameters. We observed that Spot42 and RyhB function in distinctive parameter regimes, which result in divergent mechanisms.

AB - Small regulatory RNAs (sRNAs) in eukaryotes and bacteria play an important role in the regulation of gene expression either by binding to regulatory proteins or directly to target mRNAs. Two of the best-characterized bacterial sRNAs, Spot42 and RyhB, form a complementary pair with the ribosome binding region of their target mRNAs, thereby inhibiting translation or promoting mRNA degradation. To investigate the steady-state and dynamic potential of such sRNAs, we examine the 2 key parameters characterizing sRNA regulation: the capacity to overexpress the sRNA relative to its target mRNA and the speed at which the target mRNA is irreversibly inactivated. We demonstrate different methods to determine these 2 key parameters, for Spot42 and RyhB, which combine biochemical and genetic experiments with computational analysis. We have developed a mathematical model that describes the functional properties of sRNAs with various characteristic parameters. We observed that Spot42 and RyhB function in distinctive parameter regimes, which result in divergent mechanisms.

KW - Algorithms

KW - Bacterial Proteins

KW - Gene Expression Regulation, Bacterial

KW - Models, Genetic

KW - RNA, Bacterial

KW - RNA, Messenger

KW - RNA, Untranslated

KW - Transcription, Genetic

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1073/pnas.0901466106

DO - 10.1073/pnas.0901466106

M3 - Journal article

C2 - 19541626

SN - 0027-8424

VL - 106

SP - 10655

EP - 10659

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 26

ER -