Cell cycle-dependent regulation of RNA polymerase I transcription: The nucleolar transcription factor UBF is inactive in mitosis and early G ₁

Abstract

Transcription of ribosomal RNA genes by RNA polymerase (pol) I oscillates during the cell cycle, being maximal in S and G 2 phase, repressed during mitosis, and gradually recovering during G 1 progression. We have shown that transcription initiation factor (TIF)-IB͞SL1 is inactivated during mitosis by cdc2͞cyclin B-directed phosphorylation of TAF I 110. In this study, we have monitored reactivation of transcription after exit from mitosis. We demonstrate that the pol I factor UBF is also inactivated by phosphorylation but recovers with different kinetics than TIF-IB͞SL1. Whereas TIF-IB͞SL1 activity is rapidly regained on entry into G 1 , UBF is reactivated later in G 1 , concomitant with the onset of pol I transcription. Repression of pol I transcription in mitosis and early G 1 can be reproduced with either extracts from cells synchronized in M or G 1 phase or with purified TIF-IB͞SL1 and UBF isolated in the presence of phosphatase inhibitors. The results suggest that two basal transcription factors, e.g., TIF-IB͞SL1 and UBF, are inactivated at mitosis and reactivated by dephosphorylation at the exit from mitosis and during G 1 progression, respectively.

Multiple interactions between RNA polymerase I, TIF‐IA and TAF I subunits regulate preinitiation complex assembly at the ribosomal gene promoter

“…Previous studies revealed that the shutdown of rRNA synthesis during mitosis and early G 1 phase is due to inactivation of TIF-IB/SL1 and UBF (Heix et al, 1998;Klein and Grummt, 1999). Growth-dependent regulation of Pol I, on the other hand, has been attributed to alterations in the amount or activity of TIF-IA (Buttgereit et al, 1985;Schnapp et al, 1993).…”

Human tumor suppressor p14ARF negatively regulates rRNA transcription and inhibits UBF1 transcription factor phosphorylation

“…Conditions that harm cellular metabolism are accompanied by profound, but reversible, changes in the rate of rRNA genes transcription. During cell cycle progression in mammals, rRNA transcription levels are finely regulated, high in the S and G2 phases they shut down in mitosis and progressively increase in G1 (Pardee, 1989;Grummt, 1999;Klein and Grummt, 1999). The regulation of cell growth and proliferation via the production of ribosomes can also be controlled at later stages, during rRNA processing or ribosome assembly.…”

Dynamic epigenetic states of ribosomal RNA promoters during the cell cycle

“…Our data is consistent with other reports showing that there is a large increase in pre-rRNA transcript in G 2 with decreases in G 1 . 5,46 Another report done in yeast has found that the levels of rRNA transcript peaks following replication late in S phase. 4 However, this increase during S phase was only two fold, suggesting it may be due to the duplication of the genome, while we observe a 3-4 fold increase.…”

“…49 UBF is also phosphorylated and inactivated in mitosis. 5 MBD3 undergoes phosphorylation at G 2 /M by the cell cycle dependent kinase Aurora A, 50 however it is unknown whether this affects its ability to bind DNA. SL-1 is reactivated and remains bound in G 1 , 5 which is thought to allow the basal transcriptional levels of rRNA, while acetylation and phosphorylation by cdk4/cyclin D1 and cdk2/Cyclin E&A of UBF promotes its interaction with Pol I, 6,7,13 thus allowing for increased transcription.…”

“…In yeast it was found that the levels of rRNA transcription increased late in S phase 4 while in mouse culture cells rRNA transcription was reported to peak in G 2 , shut down during mitosis, and gradually increase in G 1 . 5 These changes in transcription levels are likely due to post-translational changes in a number of factors involved in regulating rRNA transcription levels within the cell cycle. During mitosis transcription is inhibited through the phosphorylation of the TAF 1 110 subunit of SL-1 by cdk1/cyclin B.…”