Gene expression. MicroRNA control of protein expression noise

TY - JOUR

T1 - Gene expression. MicroRNA control of protein expression noise

AU - Schmiedel, Jörn M

AU - Klemm, Sandy L

AU - Zheng, Yannan

AU - Sahay, Apratim

AU - Blüthgen, Nils

AU - Marks, Debora S

AU - van Oudenaarden, Alexander

N1 - Copyright © 2015, American Association for the Advancement of Science.

PY - 2015/4/3

Y1 - 2015/4/3

N2 - MicroRNAs (miRNAs) repress the expression of many genes in metazoans by accelerating messenger RNA degradation and inhibiting translation, thereby reducing the level of protein. However, miRNAs only slightly reduce the mean expression of most targeted proteins, leading to speculation about their role in the variability, or noise, of protein expression. We used mathematical modeling and single-cell reporter assays to show that miRNAs, in conjunction with increased transcription, decrease protein expression noise for lowly expressed genes but increase noise for highly expressed genes. Genes that are regulated by multiple miRNAs show more-pronounced noise reduction. We estimate that hundreds of (lowly expressed) genes in mouse embryonic stem cells have reduced noise due to substantial miRNA regulation. Our findings suggest that miRNAs confer precision to protein expression and thus offer plausible explanations for the commonly observed combinatorial targeting of endogenous genes by multiple miRNAs, as well as the preferential targeting of lowly expressed genes.

AB - MicroRNAs (miRNAs) repress the expression of many genes in metazoans by accelerating messenger RNA degradation and inhibiting translation, thereby reducing the level of protein. However, miRNAs only slightly reduce the mean expression of most targeted proteins, leading to speculation about their role in the variability, or noise, of protein expression. We used mathematical modeling and single-cell reporter assays to show that miRNAs, in conjunction with increased transcription, decrease protein expression noise for lowly expressed genes but increase noise for highly expressed genes. Genes that are regulated by multiple miRNAs show more-pronounced noise reduction. We estimate that hundreds of (lowly expressed) genes in mouse embryonic stem cells have reduced noise due to substantial miRNA regulation. Our findings suggest that miRNAs confer precision to protein expression and thus offer plausible explanations for the commonly observed combinatorial targeting of endogenous genes by multiple miRNAs, as well as the preferential targeting of lowly expressed genes.

U2 - 10.1126/science.aaa1738

DO - 10.1126/science.aaa1738

M3 - Article

C2 - 25838385

SN - 0036-8075

VL - 348

SP - 128

EP - 132

JO - Science Magazine

JF - Science Magazine

IS - 6230

ER -