Abstract
Coupled transcription-translation (CTT) is a hallmark of prokaryotic gene expression. CTT occurs when ribosomes associate with and initiate translation of mRNAs whose transcription has not yet concluded, therefore forming “RNAP.mRNA.ribosome” complexes. CTT is a well-documented phenomenon that is involved in important gene regulation processes, such as attenuation and operon polarity. Despite the progress in our understanding of the cellular signals that coordinate CTT, certain aspects of its molecular architecture remain controversial. Additionally, new information on the spatial segregation between the transcriptional and the translational machineries in certain species, and on the capability of certain mRNAs to localize translation-independently, questions the unanimous occurrence of CTT. Furthermore, studies where transcription and translation were artificially uncoupled showed that transcription elongation can proceed in a translation-independent manner. Here, we review studies supporting the occurrence of CTT and findings questioning its extent, as well as discuss mechanisms that may explain both coupling and uncoupling, e.g., chromosome relocation and the involvement of cis- or trans-acting elements, such as small RNAs and RNA-binding proteins. These mechanisms impact RNA localization, stability, and translation. Understanding the two options by which genes can be expressed and their consequences should shed light on a new layer of control of bacterial transcripts fate.
Highlights
The conclusions that emerge from these structures are that coupling via NusG restrains RNAP motions, that the length of the intervening mRNA determines whether NusG can be involved, that expressome formation is strictly mRNAdependent, RNAP·30S complexes were previously observed (Demo et al, 2017), and that both the NusG-bridged and the collided expressomes are compatible with translation factor binding (Webster et al, 2020)
The second study, published by the Ebright lab, in addition to confirming many of the results presented by Weixlbaumer and coworkers and showing that collided expressomes are incompatible with ribosome·NusG binding, provides insights into the participation of NusA in Coupled transcription-translation (CTT) (Wang et al, 2020b)
A reassessment of RNA decay patterns unraveled that, contrary to the widespread idea that RNA decay is exponential, two-thirds of the analyzed transcripts followed a biphasic degradation pattern, with a very steep decay at short post-transcription times followed by an exponential decay at longer times (Deneke et al, 2013). These results suggest that most transcripts spend a minor fraction of their lifetime in a ribosome-free form, where they are highly vulnerable to ribonucleases until ribosomes engage in translation and slowdown mRNA decay
Summary
The fact that transcription and translation could be coupled in prokaryotes was first proposed by Stent in the mid-1960s. This model is supported by the finding that in strains harboring ribosomal mutations that slow translation, transcription elongation rates decreased and that transcription-translation rates of different genes correlated with their rare codon content, highlighting the role of translation in dictating transcription elongation (Proshkin et al, 2010) In this model, the leading ribosome equalizes transcription-translation rates by physically pushing forward the RNAP, which otherwise tends to spontaneous backtracking and/or pauses (Proshkin et al, 2010; Stevenson-Jones et al, 2020), so that CTT remains coordinated and futile transcription is prevented. Considering the ongoing discovery of (p)ppGpp-regulated processes and the tight relationship of alarmones with the metabolic status of the cell, we expect that additional pathways ensuring CTT coordination via (p)ppGpp will be discovered These complementary mechanisms, i.e., physical contacts between RNAP and the leading ribosome and alarmone-mediated coordination, account for the observed correlation between transcription and translation elongation rates under different growth conditions
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