Shapiro redux: bacterial DNA controls (Introduction)

by David Turell , Thursday, January 11, 2024, 15:42 (107 days ago) @ David Turell

Using ncRNA changes:

https://www.sciencedirect.com/science/article/abs/pii/S2451945623004415

"Commensal and pathogenic bacteria continuously evolve to survive in diverse ecological niches by efficiently coordinating gene expression levels in their ever-changing environments. Regulation through the RNA transcript itself offers a faster and more cost-effective way to adapt than protein-based mechanisms and can be leveraged for diagnostic or antimicrobial purposes. However, RNA can fold into numerous intricate, not always functional structures that both expand and obscure the plethora of roles that regulatory RNAs serve within the cell. Here, we review the current knowledge of bacterial non-coding RNAs in relation to their folding pathways and interactions. We posit that co-transcriptional folding of these transcripts ultimately dictates their downstream functions. Elucidating the spatiotemporal folding of non-coding RNAs during transcription therefore provides invaluable insights into bacterial pathogeneses and predictive disease diagnostics. Finally, we discuss the implications of co-transcriptional folding and applications of RNAs for therapeutics and drug targets.

"In order to survive and thrive, bacteria must constantly tune their metabolism and overall gene expression to adjust to their ever-changing environment and ecological niches. Because of the competition between species, it is crucial for their survival that bacteria adapt quickly to transient nutritional resources as well as external threats such as antibiotics and toxins. (my bold)

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"In bacteria, a single multi-subunit RNA polymerase (RNAP) enzyme is responsible for the synthesis of all RNA transcripts within the cell. The core enzyme forms a conserved architecture4 comprising all of the regulatory functions necessary for the efficient and accurate synthesis and folding of the transcripts during all phases of transcription, namely initiation, elongation, and termination. RNAP is subject to multiple types of regulatory processes that, in combination, determine the overall levels of expression of all genes.

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"Maintaining a temporal balance between transcription progress, folding, and RNA functional action is key to the survival of bacteria. Slight changes in the timing of transcription (too fast or too slow) therefore can have deleterious effects, leading to competitive disadvantages or even loss of viability. Examining the importance of the relative timescales of transcription and RNA folding therefore will allow for a deeper and more nuanced understanding of critical biomolecular processes.

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"ncRNAs have emerged as significant players in gene regulation in all domains of life, including bacteria. Unlike coding RNAs, which are translated into proteins, ncRNAs are not recruiting the ribosome for translation, but instead typically perform regulatory functions at the transcriptional or post-transcriptional level (Figure 1). There are diverse classes of ncRNAs, varying in length and structure, with roles encompassing regulation of basal gene expression, stress responses,

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"ncRNAs fold co-transcriptionally into intricate structures on a rugged energy landscape
Whereas a plethora of ncRNAs such as sRNAs are thought to modulate gene expression at the post-transcriptional level, increasing evidence points toward a more complex regulation that operates during the transcription process itself. RNA molecules in general, and ncRNAs such as riboswitches in particular, are complex structures folded into unique three-dimensional shapes."

Comment: this is a clear expression of why bacteria can edit their DNA so precisely. Shapiro's work is not mentioned.