The 5′ terminal oligopyrimidine tract of human elongation factor 1A-1 gene functions as a transcriptional initiator and produces a variable number of Us at the transcriptional level

Shibui, Akiko; Ohmori, Yuki; Yoshida, Kenichi; Imai, Jun‐ichi; Oosuga, Ikurou; Iidaka, Makoto; Suzuki, Yutaka; Mizushima‐Sugano, Junko; Yoshitomo-Nakagawa, Kiyomi; Sugano, Sumio

doi:10.1016/s0378-1119(03)00583-3

Cited by 12 publications

(12 citation statements)

References 27 publications

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“…In multicellular organisms, since it is the only known sequence element conserved among all RP genes, the 5'TOP motif is considered a key regulatory element for the coordinated control of RP synthesis. Previous studies suggest that the TOP motif provides control of both the transcription of TOP-genes (Parry et al, 2010;Shibui-Nihei et al, 2003) and the translation of TOP-mRNAs (Fonseca et al, 2018;Gentilella et al, 2017;Hamilton et al, 2006;Lahr et al, 2017;Meyuhas and Kahan, 2015;Patursky-Polischuk et al, 2014). A linear correlation of the activity of the luciferase reporters containing the Rpl28 promoter and the abundance of their transcripts (Fig.…”

Section: Discussionmentioning

confidence: 99%

Control of ribosomal protein synthesis by Microprocessor complex

Jiang

Prabhakar

Voorn

et al. 2020

Preprint

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Ribosome biogenesis in eukaryotes requires stoichiometric production and assembly of 80 ribosomal proteins (RPs) and 4 ribosomal RNAs, and its rate must be coordinated with cellular growth. The indispensable regulator of RP biosynthesis is the 5'-terminal oligopyrimidine (TOP) motif, spanning the transcription start site of all RP genes. Here we show that the Microprocessor complex, previously linked to the first step of processing microRNAs (miRNAs), coregulates RP expression by binding the TOP motif of nascent RP mRNAs and stimulating transcription elongation via resolution of DNA/RNA hybrids. Cell growth arrest triggers nuclear export and degradation of the Microprocessor protein Drosha by the E3 ubiquitin ligase Nedd4, accumulation of DNA/RNA hybrids at RP gene loci, decreased RP synthesis, and ribosome deficiency, hence synchronizing ribosome production with cell growth. Conditional deletion of Drosha in erythroid progenitors phenocopies human ribosomopathies, in which ribosomal insufficiency leads to anemia. Outlining a miRNA-independent role of the Microprocessor complex at the interphase between cell growth and ribosome biogenesis offers a new paradigm by which cells alter their protein biosynthetic capacity and cellular metabolism.in response to the change in cellular growth environment remains to be identified (Meyuhas and Kahan, 2015; Patursky-Polischuk et al., 2014).During transcription, a three-stranded nucleic acid structure known as an R-loop spontaneously forms(García-Muse and Aguilera, 2019). It is composed of a DNA/RNA hybrid (a single-stranded template DNA (ssDNA) hybridized with a nascent mRNA) and an associated non-template ssDNA (García-Muse and Aguilera, 2019;Sanz and Chédin, 2019;Sanz et al., 2016). R-loops are critical modulator of gene expression and DNA repair (García-Muse and Aguilera, 2019;Sanz and Chédin, 2019;Sanz et al., 2016), and their extended persistence during transcription is inhibitory to gene expression (Gowrishankar et al., 2013;Nudler, 2012). The abundance of R-loops is determined by the balance between its formation and resolution of DNA/RNA hybrids and various factors, including transcription factors, helicases, ribonucleases, topoisomerases, chromatin remodelers, proteins in DNA repair and RNA surveillance, have been identified to control R-loop homeostasis(García-Muse and Aguilera, 2019). Deregulation of R-loops, which results in aberrant gene expression and chromatin structure, increased DNA breaks, and genome instability, contributes to human disease, including neurological disorders and tumorigenesis (García-Muse and Aguilera, 2019;Groh and Gromak, 2014;Sanz et al., 2016).The Microprocessor complex comprises two core components, the ribonuclease (RNase) III Drosha and its cofactor Dgcr8. It is essential for the biogenesis of most microRNAs (miRNAs), short RNAs that repress gene expression by binding to messenger RNAs and targeting them for degradation and/or preventing their translation (Han et al., 2004;Siomi and Siomi, 2010). The Microprocessor localizes predom...

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Section: Discussionmentioning

confidence: 99%

Control of ribosomal protein synthesis by Microprocessor complex

Jiang

Prabhakar

Voorn

et al. 2020

Preprint

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“…This is also important since the 5 0 terminal oligopyrimidine tract of the EF1a promoter, which is present in the SIVmac239-EF1a/STR transcripts, has been shown to function as a transcriptional initiator. 44 It has been shown that the sequence G C1 GGTCT represents the core of a HIV-1 initiator element (INR) required for Tat-responsive transcription. 18 This sequence differs significantly from mammalian INR elements and is surprisingly not conserved in SIVmac239 (the corresponding sequence is C C1 AGTCG).…”

Section: Discussionmentioning

confidence: 99%

Anti-termination by SIV Tat Requires Flexibility of the Nascent TAR Structure

Sommer

Vartanian

Wachsmuth

et al. 2004

Journal of Molecular Biology

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“…37 Another element with an INR positional bias is the pyrimidine-rich TOP element present in many protein biogenesis genes. 38,39 The TOP element was recently reported to be active in Drosophila as well. 40 Even though a substantial fraction of promoters lack both TATA-box and INR there is only a limited number of characterized core elements that function independently of a TATAbox or INR.…”

Section: Introductionmentioning

confidence: 99%

The unexpected traits associated with core promoter elements

Dikstein

2011

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The core promoter of eukaryotic coding and non-coding genes that are transcribed by RNA polymerase II (RNAP II) is composed of DNA elements surrounding the transcription start site. These elements serve as the docking site of the basal transcription machinery and have an important role in determining the position and directing the rate of transcription initiation. This review summarizes the current knowledge about core promoter elements and focuses on several unexpected links between core promoter structure and certain gene features. These include the association between the presence or absence of a TATA-box and gene length, gene structure, gene function, evolution rate and transcription elongation. Key words: core promoter, TATA-box, TATA-less promoter, gene length, transcription elongation Core Promoter ElementsThe first core promoter element to be described in eukaryotes was the TATA-box. 3 The TATA-box is a highly conserved element, strictly located between -35 to -25 relative to the TSS (designated +1) in most eukaryotes. The TATA-box, which was once thought to be a universal element, is present in a smaller fraction of RNAP II genes than initially estimated ( Table 1): between 20-46% in yeast (depending on the definition of the TATAbox sequence), 4,5 ~30% of Drosophila genes 6 and up to 35% of human genes.7-10 The major core promoter-binding factor is TFIID, a large complex consisting of the TATA-binding protein (TBP) and 13 associated factors called TAFs. The TATA-box is directly recognized and bound by TBP, while the TAFs interact with sequences upstream and downstream to the TATA-box.

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The 5′ terminal oligopyrimidine tract of human elongation factor 1A-1 gene functions as a transcriptional initiator and produces a variable number of Us at the transcriptional level

Cited by 12 publications

References 27 publications

Control of ribosomal protein synthesis by Microprocessor complex

Control of ribosomal protein synthesis by Microprocessor complex

Anti-termination by SIV Tat Requires Flexibility of the Nascent TAR Structure

The unexpected traits associated with core promoter elements

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