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, Rivka Dikstein
2013 Nature Communications  
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 proteincoding genes is associated with increased sensitivity to slow RNA polymerase II. Promoters driven by TATA box or NF-kB 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
more » ... increases. This phenomenon is associated with a delay in miR-146a induction by NF-kB. 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-kB 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.
doi:10.1038/ncomms3118 pmid:23831825 fatcat:f2av4beysbhtzjt2q2mm3zg6oe