The intricate relationship between transcription and translation

Abstract

Two conserved processes express the genetic information of all organisms. First, DNA is transcribed into a messenger RNA (mRNA) by the multisubunit enzyme RNA polymerase (RNAP). Second, the mRNA directs protein synthesis, when the ribosome translates its nucleotide sequence to amino acids using the genetic code. Because these two processes are so fundamental, a multitude of regulatory processes have evolved to regulate them. Most examples involve regulation of either transcription or translation. In PNAS, Chatterjee et al. (1) instead describe a complex and intricate regulatory process in which transcription and translation are concurrently regulated by each other. Transcription and translation are commonly viewed as separate. In eukaryotes, their respective confinement to the nucleus and cytoplasm enforces this. Yet, prokaryotes have no such barrier, and newly synthesized mRNAs are translated while they are still being transcribed. RNAP and the trailing ribosome are therefore in close spatial proximity, allowing each to influence the activity of the other. The possibility of a physical connection that could support functional coupling was proposed in 1964 by Marshall Nirenberg’s laboratory based on biochemical experiments (2). They highlighted the potential importance of regulatory processes that simultaneously affect both transcription and translation. Electron micrographs of ruptured Escherichia coli cells, commonly termed “Miller spreads,” confirmed the close proximity between RNAP and the trailing ribosome (3). The role and mechanism of coupling have received renewed interest over the past 10 y. Biochemical and structural approaches alongside new measurements of gene expression rates in vivo have clarified several important aspects. Early studies had demonstrated that translation can release RNAP from regulatory pauses (4). This mechanism, part of a process known as attenuation, had been described in the context of the leader sequences of specific operons. Yet more recent evidence points to additional genome-wide mechanisms of … [↵][1]1To whom correspondence may be addressed. Email: albert.weixlbaumer{at}igbmc.fr. [1]: #xref-corresp-1-1

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