Disparity between microRNA levels and promoter strength is associated with initiation rate and Pol II pausing

Nadav Marbach-Bar, Amitai Ben-Noon, Shaked Ashkenazi, Ana Tamarkin-Ben Harush, Tali Avnit-Sagi, Michael D. Walker and Rivka Dikstein ()
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Nadav Marbach-Bar: The Weizmann Institute of Science
Amitai Ben-Noon: The Weizmann Institute of Science
Shaked Ashkenazi: The Weizmann Institute of Science
Ana Tamarkin-Ben Harush: The Weizmann Institute of Science
Tali Avnit-Sagi: The Weizmann Institute of Science
Michael D. Walker: The Weizmann Institute of Science
Rivka Dikstein: The Weizmann Institute of Science

Nature Communications, 2013, vol. 4, issue 1, 1-12

Abstract: Abstract MicroRNAs are transcribed by RNA polymerase II but the transcriptional features influencing their synthesis are poorly defined. Here we report that a TATA box in microRNA and protein-coding genes is associated with increased sensitivity to slow RNA polymerase II. Promoters driven by TATA box or NF-κB elicit high re-initiation rates, but paradoxically lower microRNA levels. MicroRNA synthesis becomes more productive by decreasing the initiation rate, but less productive when the re-initiation rate increases. This phenomenon is associated with a delay in miR-146a induction by NF-κB. Finally, we demonstrate that microRNAs are remarkably strong pause sites. Our findings suggest that lower efficiency of microRNA synthesis directed by TATA box or NF-κB is a consequence of frequent transcription initiations that lead to RNA polymerase II crowding at pause sites, thereby increasing the chance of collision and premature termination. These findings highlight the importance of the transcription initiation mechanism for microRNA synthesis, and have implications for TATA-box promoters in general.

Date: 2013
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DOI: 10.1038/ncomms3118

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