Synthetic 5' UTRs Can Either Up- or Downregulate Expression upon RNA-Binding Protein Binding.

Abstract:

:The construction of complex gene-regulatory networks requires both inhibitory and upregulatory modules. However, the vast majority of RNA-based regulatory "parts" are inhibitory. Using a synthetic biology approach combined with SHAPE-seq, we explored the regulatory effect of RNA-binding protein (RBP)-RNA interactions in bacterial 5' UTRs. By positioning a library of RNA hairpins upstream of a reporter gene and co-expressing them with the matching RBP, we observed a set of regulatory responses, including translational stimulation, translational repression, and cooperative behavior. Our combined approach revealed three distinct states in vivo: in the absence of RBPs, the RNA molecules can be found in either a molten state that is amenable to translation or a structured phase that inhibits translation. In the presence of RBPs, the RNA molecules are in a semi-structured phase with partial translational capacity. Our work provides new insight into RBP-based regulation and a blueprint for designing complete gene-regulatory circuits at the post-transcriptional level.

journal_name

Cell Syst

journal_title

Cell systems

authors

Katz N,Cohen R,Solomon O,Kaufmann B,Atar O,Yakhini Z,Goldberg S,Amit R

doi

10.1016/j.cels.2019.04.007

subject

Has Abstract

pub_date

2019-07-24 00:00:00

pages

93-106.e8

issue

1

eissn

2405-4712

issn

2405-4720

pii

S2405-4712(19)30149-8

journal_volume

9

pub_type

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