RT Journal Article
SR Electronic
T1 Hfq CLASH uncovers sRNA-target interaction networks enhancing adaptation to nutrient availability
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 481986
DO 10.1101/481986
A1 Ira A. Iosub
A1 Marta Marchioretto
A1 Brandon Sy
A1 Stuart McKellar
A1 Karen J. Nieken
A1 Rob W. van Nues
A1 Jai J. Tree
A1 Gabriella Viero
A1 Sander Granneman
YR 2018
UL http://biorxiv.org/content/early/2018/11/29/481986.abstract
AB A reason microorganisms are so successful is their ability to rapidly adapt to constantly changing environments. Bacterial small RNAs (sRNAs) play an important role in adaptive responses by shaping gene expression profiles and integrating multiple regulatory pathways. This enables microorganisms to more efficiently counteract environmental insults than could be achieved by simply switching transcription factors on and off. Although a plethora of sRNAs have been identified, the majority have not been functionally characterized and their relative contribution in regulating adaptive responses remains unclear. To better understand how Escherichia coli acclimatizes to changes in nutrient availability, we performed UV cross-linking, ligation and sequencing of hybrids (CLASH) to uncover sRNA-target interaction networks. Using this proximity-dependent RNA-RNA ligation method, we uncovered thousands of sRNA-target duplexes associated with the RNA chaperone Hfq at specific growth stages, many of which have not been described before. Our work revealed that 3′UTR-derived sRNAs and sRNA-sRNA interactions are more prevalent than previously anticipated. We uncovered sRNA-target interaction networks that play a role in adaptation to changes in nutrient availability by enhancing the uptake of nutrients from the environment. We describe detailed functional analyses of a novel sRNA (MdoR), the first example of a bacterial 3′UTR-derived sRNA that functions as part of a mixed coherent feed forward loop. MdoR enhances the effectiveness of maltose uptake by (a) inactivating repressive pathways that blocks the accumulation of specific maltose transporters and (b) by reducing the flux of general porins to the outer membrane. Our work suggests that many mRNAs encode regulatory sRNAs embedded within their 3′UTRs, allowing direct regulatory interactions between functionally related mRNAs. Small RNA sponging interactions appear frequently and reveal that major nutritional stress responses are coordinated post-transcriptionally. This provides striking examples of how cells utilize sRNA regulatory networks to integrate multiple signals and regulatory pathways to enhance nutrient stress adaptation.