The human Y4 small cytoplasmic RNA gene is controlled by upstream elements and resides on chromosome 7 with all other hY scRNA genes

Maraia, Richard J; Sasaki-Tozawa, Noriko; Driscoll, Claire; Green, Eric D.; Darlington, Gretchen J.

doi:10.1093/nar/22.15.3045

Cited by 43 publications

(28 citation statements)

References 42 publications

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“…However, La was detected at these genes, along with pol III. Brf1 was not found, consistent with the prediction, based on sequence, that these genes have type III promoters (41,42). We have also tested 5S rRNA and tRNA Leu genes and again saw no association of Ro, although La is clearly detected (Fig.…”

Section: The Human Autoantigen Ro Is Not Found Associated With Pol Iii-supporting

confidence: 86%

Human La is found at RNA polymerase III-transcribed genes in vivo

Fairley

Kantidakis

Kenneth

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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The human La autoantigen can bind to nascent RNA transcripts and has also been postulated to act as an RNA polymerase III (pol III) transcription initiation and termination factor. Here, we show by chromatin immunoprecipitation (ChIP) that La is associated with pol III-transcribed genes in vivo. In contrast, the Ro autoantigen, which can also bind pol III transcripts, is not found at these genes. The putative pol III transcription factors NF1 and TFIIA are also not detected at class III genes. Binding of La remains when transcription is repressed at mitosis and does not correlate with the presence of polymerase at the gene. However, gene occupancy depends on the phosphorylation status of La, with the less prevalent, unphosphorylated form being found selectively on pol III templates.La ͉ NF1 ͉ TFIIA ͉ chromatin immunoprecipitation ͉ RNA polymerase III transcription R NA polymerase III (pol III) is responsible for the production of a number of short, untranslated RNAs that are essential for cellular growth; pol III transcription is therefore a major determinant of the biosynthetic capacity of cells (reviewed in refs. 1 and 2). The key to understanding how this influence is regulated is the identification of factors that can control expression. Pol III promoters can be divided into three types that utilize different transcription factors for their activity. Type 1 and 2 promoters, exemplified by the 5S rRNA and tRNA promoters, respectively, recruit TFIIIA and͞or TFIIIC, through binding to sequence-specific elements within the gene (reviewed in refs. 3 and 4). TFIIIC in turn recruits a TFIIIB complex containing Brf1, TBP, and Bdp1, which is able to recruit the polymerase through protein-protein interactions. In contrast, type 3 promoters, such as that for U6 small nuclear RNA (snRNA), contain gene external elements that are recognized by the SNAPc complex and TFIIIB (4); however, the TFIIIB in this case differs from that used for type 1 and type 2 promoters in utilizing Brf2 instead of Brf1 (4, 5). In addition to these basal transcription factors, a number of other proteins have been found to influence pol III transcription in mammals. Some of these regulators have been shown to associate with pol III templates in vivo, including c-Myc (6), RB (7), ␤-actin (8), and the protein kinase CK2 (9, 10). However, there are a number of other proteins, including La, TFIIA and NF1, for which a role in pol III transcription has been suggested from experiments in vitro, but which has not been confirmed in vivo.The human autoantigen La is a highly abundant protein found associated with newly synthesized pol III products (11,12). La binds to nascent pol III transcripts through the UUU-OH at their 3Ј ends, which corresponds to the pol III termination signal, and also has affinity for their 5Ј ends (13-15). One of the functions of La is in the stabilization of these transcripts, which promotes their processing to the mature forms (16). However, La has also been reported to have effects on pol III transcription. Immunodepletion of La...

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Section: The Human Autoantigen Ro Is Not Found Associated With Pol Iii-supporting

confidence: 86%

Human La is found at RNA polymerase III-transcribed genes in vivo

Fairley

Kantidakis

Kenneth

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…A corresponding increase in hdm2 transcript levels was seen in the nuclear pellets (P) after U0126 exposure. Semiquantitative PCR detection of the small cytoplasmic RNA scRNA hY4 (45) confirmed that the cell lysis technique efficiently separated cytoplasmic RNA from the nuclear pellet, whereas gapdh mRNA was present in both fractions. After U0126 treatment, hdm2 mRNA clearly becomes associated with the insoluble pellet.…”

Section: Pharmacological Inhibition Of Mek Activity Suppresses Hdm2 Pmentioning

confidence: 74%

MEK-ERK Signaling Controls Hdm2 Oncoprotein Expression by Regulating hdm2 mRNA Export to the Cytoplasm

Phelps

Phillips

Darley

et al. 2005

Journal of Biological Chemistry

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The physical and functional interaction between the transcription factor p53 and its negative regulatory partner protein Hdm2 (Mdm2 in mouse) is a key point of convergence of multiple signaling pathways that regulates cell proliferation and survival. hdm2 mRNA transcription is induced by p53, forming the basis of an auto-regulatory feedback loop. Growth and survival factor-activated Ras-Raf-MEK-ERK signaling can also regulate Hdm2 expression independently of p53, contributing to the pro-survival effect of these factors. In murine fibroblasts, this occurs through the regulation of mdm2 mRNA transcription. Here we show that, in human breast cancer epithelial cells, MEK-dependent regulation of Hdm2 expression also occurs at a post-transcriptional level. Pharmacological blockade of MEK activity in T47D cells inhibits Hdm2 protein synthesis by 80 -90%. This occurs in the absence of changes in the expression of the major hdm2-P1 mRNA transcript and only an ϳ40% reduction in hdm2-P2 transcript levels. The amounts of both transcripts that are associated with polyribosomes and are, hence, being actively translated are reduced by >80% by the MEK inhibitor, U0126. We show here that this is due to the inhibition of hdm2 mRNA export from the nucleus when MEK activity is inhibited. In MCF-7 breast cancer cells that express wild-type p53, Hdm2 is required to suppress p53-dependent transcription when MEK kinase is active. Regulation of the nuclear export of hdm2 mRNA provides, therefore, a mechanism whereby mitogen-stimulated cells avoid p53-dependent cell cycle arrest or apoptosis by maintaining the dynamic equilibrium of the Hdm2-p53 feedback loop.

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“…In human cells, four Y RNAs (hY1, hY3, hY4, and hY5 RNA) are transcribed by RNA polymerase III from single copy genes, clustered into a single locus on chromosome 7 (Hendrick et al 1981;Maraia et al 1994Maraia et al , 1996Matera et al 1995). Y RNAs are not modified and fold into characteristic stem-loop structures ( Fig.…”

Section: Introductionmentioning

confidence: 99%

A conserved motif of vertebrate Y RNAs essential for chromosomal DNA replication

Gardiner¹,

Christov²,

Langley³

et al. 2009

RNA

132

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Noncoding Y RNAs are required for the reconstitution of chromosomal DNA replication in late G1 phase template nuclei in a human cell-free system. Y RNA genes are present in all vertebrates and in some isolated nonvertebrates, but the conservation of Y RNA function and key determinants for its function are unknown. Here, we identify a determinant of Y RNA function in DNA replication, which is conserved throughout vertebrate evolution. Vertebrate Y RNAs are able to reconstitute chromosomal DNA replication in the human cell-free DNA replication system, but nonvertebrate Y RNAs are not. A conserved nucleotide sequence motif in the double-stranded stem of vertebrate Y RNAs correlates with Y RNA function. A functional screen of human Y1 RNA mutants identified this conserved motif as an essential determinant for reconstituting DNA replication in vitro. Double-stranded RNA oligonucleotides comprising this RNA motif are sufficient to reconstitute DNA replication, but corresponding DNA or random sequence RNA oligonucleotides are not. In intact cells, wild-type hY1 or the conserved RNA duplex can rescue an inhibition of DNA replication after RNA interference against hY3 RNA. Therefore, we have identified a new RNA motif that is conserved in vertebrate Y RNA evolution, and essential and sufficient for Y RNA function in human chromosomal DNA replication.

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The human Y4 small cytoplasmic RNA gene is controlled by upstream elements and resides on chromosome 7 with all other hY scRNA genes

Cited by 43 publications

References 42 publications

Human La is found at RNA polymerase III-transcribed genes in vivo

Human La is found at RNA polymerase III-transcribed genes in vivo

MEK-ERK Signaling Controls Hdm2 Oncoprotein Expression by Regulating hdm2 mRNA Export to the Cytoplasm

A conserved motif of vertebrate Y RNAs essential for chromosomal DNA replication

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