A Post-Transcriptional Feedback Mechanism for Noise Suppression and Fate Stabilization.
Cell
; 173(7): 1609-1621.e15, 2018 06 14.
Article
in En
| MEDLINE
| ID: mdl-29754821
ABSTRACT
Diverse biological systems utilize fluctuations ("noise") in gene expression to drive lineage-commitment decisions. However, once a commitment is made, noise becomes detrimental to reliable function, and the mechanisms enabling post-commitment noise suppression are unclear. Here, we find that architectural constraints on noise suppression are overcome to stabilize fate commitment. Using single-molecule and time-lapse imaging, we find that-after a noise-driven event-human immunodeficiency virus (HIV) strongly attenuates expression noise through a non-transcriptional negative-feedback circuit. Feedback is established through a serial cascade of post-transcriptional splicing, whereby proteins generated from spliced mRNAs auto-deplete their own precursor unspliced mRNAs. Strikingly, this auto-depletion circuitry minimizes noise to stabilize HIV's commitment decision, and a noise-suppression molecule promotes stabilization. This feedback mechanism for noise suppression suggests a functional role for delayed splicing in other systems and may represent a generalizable architecture of diverse homeostatic signaling circuits.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA, Messenger
/
HIV-1
/
Feedback, Physiological
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Cell
Year:
2018
Type:
Article
Affiliation country:
United States