4.6 Review

Coupling Between Production of Ribosomal RNA and Maturation: Just at the Beginning

Journal

FRONTIERS IN MOLECULAR BIOSCIENCES
Volume 8, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fmolb.2021.778778

Keywords

RNA polymerase I (Pol I); ribosomal RNA (rRNA) processing; transcription; termination of transcription; ribosomal RNA (rRNA) genes; RNA folding; premature termination of transcription

Funding

  1. Fondation ARC pour la Recherche sur le Cancer,

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The study highlights the coupling between rRNA production and nascent rRNA folding, showing that RNA folding acts as an anti-pausing mechanism and favors transcription elongation. Defects in co-transcriptional folding of rRNA may induce Pol I pausing, and premature termination of transcription can potentially control rRNA production in vivo.
Ribosomal RNA (rRNA) production represents the most active transcription in the cell. Synthesis of the large rRNA precursors (35S/47S in yeast/human) is achieved by up to hundreds of RNA polymerase I (Pol I) enzymes simultaneously transcribing a single rRNA gene. In this review, we present recent advances in understanding the coupling between rRNA production and nascent rRNA folding. Mapping of the distribution of Pol I along ribosomal DNA at nucleotide resolution, using either native elongating transcript sequencing (NET-Seq) or crosslinking and analysis of cDNAs (CRAC), revealed frequent Pol I pausing, and CRAC results revealed a direct coupling between pausing and nascent RNA folding. High density of Pol I per gene imposes topological constraints that establish a defined pattern of polymerase distribution along the gene, with a persistent spacing between transcribing enzymes. RNA folding during transcription directly acts as an anti-pausing mechanism, implying that proper folding of the nascent rRNA favors elongation in vivo. Defects in co-transcriptional folding of rRNA are likely to induce Pol I pausing. We propose that premature termination of transcription, at defined positions, can control rRNA production in vivo.

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