Article ; Online: Base J represses genes at the end of polycistronic gene clusters in Leishmania major by promoting RNAP II termination.
2016 Volume 101, Issue 4, Page(s) 559–574
Abstract: ... by the modified DNA base J. Previous work has established a role of base J in promoting RNA polymerase II ... termination in Leishmania spp. where the loss of J leads to termination defects and transcription ... whether read through transcription is detrimental to cell growth, thus explaining the essential nature of J ...
| Abstract | The genomes of kinetoplastids are organized into polycistronic gene clusters that are flanked by the modified DNA base J. Previous work has established a role of base J in promoting RNA polymerase II termination in Leishmania spp. where the loss of J leads to termination defects and transcription into adjacent gene clusters. It remains unclear whether these termination defects affect gene expression and whether read through transcription is detrimental to cell growth, thus explaining the essential nature of J. We now demonstrate that reduction of base J at specific sites within polycistronic gene clusters in L. major leads to read through transcription and increased expression of downstream genes in the cluster. Interestingly, subsequent transcription into the opposing polycistronic gene cluster does not lead to downregulation of sense mRNAs. These findings indicate a conserved role for J regulating transcription termination and expression of genes within polycistronic gene clusters in trypanosomatids. In contrast to the expectations often attributed to opposing transcription, the essential nature of J in Leishmania spp. is related to its role in gene repression rather than preventing transcriptional interference resulting from read through and dual strand transcription. |
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| MeSH term(s) | Gene Expression Regulation ; Glucosides/genetics ; Glucosides/metabolism ; Leishmania major/enzymology ; Leishmania major/genetics ; Leishmania major/metabolism ; Multigene Family ; RNA Polymerase II/genetics ; RNA Polymerase II/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Transcription, Genetic/genetics ; Uracil/analogs & derivatives ; Uracil/metabolism |
| Chemical Substances | Glucosides ; RNA, Messenger ; 5-((glucopyranosyloxy)methyl)uracil (53910-96-6) ; Uracil (56HH86ZVCT) ; RNA Polymerase II (EC 2.7.7.-) |
| Language | English |
| Publishing date | 2016-06-01 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 619315-8 |
| ISSN | 1365-2958 ; 0950-382X |
| ISSN (online) | 1365-2958 |
| ISSN | 0950-382X |
| DOI | 10.1111/mmi.13408 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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