Abstract
The role of post-transcriptional RNA modification is of growing interest. One example is the addition of non-templated uridine residues to the 3' end of transcripts. In mammalian systems, uridylation is integral to cell cycle control of histone mRNA levels. This regulatory mechanism is dependent on the nonsense-mediated decay (NMD) component, Upf1, which promotes histone mRNA uridylation and degradation in response to the arrest of DNA synthesis. We have identified a similar system in Aspergillus nidulans, where Upf1 is required for the regulation of histone mRNA levels. However, other NMD components are also implicated, distinguishing it from the mammalian system. As in human cells, 3' uridylation of histone mRNA is induced upon replication arrest. Disruption of this 3' tagging has a significant but limited effect on histone transcript regulation, consistent with multiple mechanisms acting to regulate mRNA levels. Interestingly, 3' end degraded transcripts are also subject to re-adenylation. Both mRNA pyrimidine tagging and re-adenylation are dependent on the same terminal-nucleotidyltransferases, CutA, and CutB, and we show this is consistent with the in vitro activities of both enzymes. Based on these data we argue that mRNA 3' tagging has diverse and distinct roles associated with transcript degradation, functionality and regulation.
Highlights
Post-transcriptional modification of mRNA has emerged as a key means of controlling functionality and expression (Nachtergaele and He, 2018)
We have previously shown that both normal transcripts with shortened poly(A) tails and aberrant transcripts containing a premature termination codon (PTC), undergo 3′-pyrimidine tagging in A. nidulans (Morozov et al, 2010; 2012) which is consistent with subsequent findings in mammalian systems (Chang et al, 2014; Kurosaki et al, 2018)
To determine if cell cycle regulation of histone encoding transcripts in fungi involves a similar mechanism to that described in human cells, we investigated the role of mRNA tagging and the nonsense-mediated decay (NMD) component, Upf1, in A. nidulans
Summary
Post-transcriptional modification of mRNA has emerged as a key means of controlling functionality and expression (Nachtergaele and He, 2018). In human cells the NMD component Upf is directly involved in the regulation of histone mRNA degradation in response to HU treatment (Kaygun and Marzluff, 2005b; Mullen and Marzluff, 2008) This appears to be the case in A. nidulans, as HU induced repression of both ht2A and ht3A was significantly diminished in the mutant strain deleted for upf (Figure 1). To determine if other NMD components play a role in the regulation of histone transcript levels we tested strains disrupted for two additional NMD factors, nmdA/upf (Morozov et al, 2006) and upf (AN0505) In both cases, the mutant strains exhibited a diminished regulatory response, the effect of Δupf was only significant for ht3A. In the case of CutA the limited adenylation activity when the terminal residue is a C or U may serve to clearly delineate the adenylation and uridylation activities such that when required CutA can effectively promote addition of poly-U tails to transcripts as seen for the histone transcripts (Figure 3 and Table S1)
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