Upstream binding transcription factor (UBTF), or upstream binding factor (UBF), is a protein that in humans is encoded by the UBTF gene. [5] [6]
Upstream binding transcription factor (UBTF), or upstream binding factor (UBF), is a protein that in humans is encoded by the UBTF gene. [5] [6]
In humans, the UBTF gene encodes a 764 amino acid protein and is located on chromosome 17 at position q21.31. [7] [8] In mice, UBTF is found on chromosome 11 [ citation needed ].
UBTF contains six high mobility group boxes (HMG-boxes) that allow it to bind to DNA. [9] UBTF also contains a hyperacidic carboxy-terminal domain, which is required for transcription activation, and a helix-gap-helix dimersation motif (as UBTF is thought to often act as a dimer). [9] [10]
In humans, alternative splicing can give rise to either the UBTF1 or UBTF2 isoform which are 97 kD and 94 kD in mass, respectively [11] UBTF2 lacks exon 8 of the larger UBTF1 isoform which encodes a portion of HMG Box 2. [12]
UBTF is a transcription factor required for expression of the 18S, 5.8S, and 28S ribosomal RNAs, along with SL1 (a complex of TBP (MIM 600075) and three TBP-associated factors or 'TAFs')[ citation needed ].
UBTF is a nucleolar phosphoprotein with both DNA binding and transactivation domains. Sequence-specific DNA binding to the core and upstream control elements of the human rRNA promoter is mediated through several HMG boxes. [13] [supplied by OMIM] [6]
In vertebrates, UBTF plays a crucial role in maintaining rDNA chromatin in a euchromatic state. Consequently, UBTF binding is one of the characteristics of euchromatic, transcriptionally active rDNA repeats. [14]
UBTF2 has been found to regulate mRNA transcription by RNA Polymerase II. [9]
UBTF may have a role in cancer. Increased UBF binding to rDNA has been observed in cancer cells and is associated with elevated rDNA transcription and tumor cell survival. [15] Supporting this, it was found that cisplatin, a chemotherapy drug, can displace UBTF from rDNA, causing a reduction in rRNA synthesis and subsequent p53-independent apoptosis. [16]
Additionally, UBTF has been found to facilitate melanoma by promoting GIT1 expression which, in turn, activates MEK1/2-ERK1/2 signaling pathways. [17]
UBTF may also be important to neurological functioning. A de novo gain-of-function mutation to UBTF (c.628G>A) has been found to cause developmental neuroregression. [12] This mutation replaces glutamic acid with lysine at position 210 of the polypeptide chain (p.Glu210Lys) which results in a stronger UBTF interaction with DNA. [18] In 2022, another likely pathogenic variant (Gln203Arg) was identified in a proband with severe early-onset developmental delay.. [19]
UBTF has been shown to interact with:
The nucleolus is the largest structure in the nucleus of eukaryotic cells. It is best known as the site of ribosome biogenesis, which is the synthesis of ribosomes. The nucleolus also participates in the formation of signal recognition particles and plays a role in the cell's response to stress. Nucleoli are made of proteins, DNA and RNA, and form around specific chromosomal regions called nucleolar organizing regions. Malfunction of nucleoli can be the cause of several human conditions called "nucleolopathies" and the nucleolus is being investigated as a target for cancer chemotherapy.
Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules called non-coding RNAs (ncRNAs). mRNA comprises only 1–3% of total RNA samples. Less than 2% of the human genome can be transcribed into mRNA, while at least 80% of mammalian genomic DNA can be actively transcribed, with the majority of this 80% considered to be ncRNA.
In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA (transcription), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from altering the number of copies of RNA that are transcribed, to the temporal control of when the gene is transcribed. This control allows the cell or organism to respond to a variety of intra- and extracellular signals and thus mount a response. Some examples of this include producing the mRNA that encode enzymes to adapt to a change in a food source, producing the gene products involved in cell cycle specific activities, and producing the gene products responsible for cellular differentiation in multicellular eukaryotes, as studied in evolutionary developmental biology.
The preinitiation complex is a complex of approximately 100 proteins that is necessary for the transcription of protein-coding genes in eukaryotes and archaea. The preinitiation complex positions RNA polymerase II at gene transcription start sites, denatures the DNA, and positions the DNA in the RNA polymerase II active site for transcription.
RNA polymerase 1 is, in higher eukaryotes, the polymerase that only transcribes ribosomal RNA, a type of RNA that accounts for over 50% of the total RNA synthesized in a cell.
In eukaryote cells, RNA polymerase III is a protein that transcribes DNA to synthesize 5S ribosomal RNA, tRNA and other small RNAs.
Treacle protein is a protein that in humans is encoded by the TCOF1 gene.
Transcription factor II B (TFIIB) is a general transcription factor that is involved in the formation of the RNA polymerase II preinitiation complex (PIC) and aids in stimulating transcription initiation. TFIIB is localised to the nucleus and provides a platform for PIC formation by binding and stabilising the DNA-TBP complex and by recruiting RNA polymerase II and other transcription factors. It is encoded by the TFIIB gene, and is homologous to archaeal transcription factor B and analogous to bacterial sigma factors.
DNA-directed RNA polymerases I and III subunit RPAC1 is a protein that in humans is encoded by the POLR1C gene.
DNA-directed RNA polymerase I subunit RPA49 is an enzyme that in humans is encoded by the POLR1E gene.
DNA-directed RNA polymerase I subunit RPA2 is an enzyme that in humans is encoded by the POLR1B gene.
TATA box-binding protein-associated factor RNA polymerase I subunit C is an enzyme that in humans is encoded by the TAF1C gene.
TATA box-binding protein-associated factor RNA polymerase I subunit A is an enzyme that in humans is encoded by the TAF1A gene.
RNA polymerase I-specific transcription initiation factor RRN3 is an enzyme that in humans is encoded by the RRN3 gene.
DNA-directed RNA polymerase I subunit RPA1 is an enzyme that in humans is encoded by the POLR1A gene.
General transcription factor IIF subunit 2 is a protein that in humans is encoded by the GTF2F2 gene.
TATA box-binding protein-associated factor RNA polymerase I subunit B is an enzyme that in humans is encoded by the TAF1B gene.
Polymerase I and transcript release factor, also known as Cavin1, Cavin-1 or PTRF, is a protein which in humans is encoded by the PTRF gene.
NAD-dependent deacetylase sirtuin 7 is an enzyme that in humans is encoded by the SIRT7 gene. SIRT7 is member of the mammalian sirtuin family of proteins, which are homologs to the yeast Sir2 protein.
Selective factor 1 is a transcription factor that binds to the promoter of genes and recruits a preinitiation complex to which RNA polymerase I will bind to and begin the transcription of ribosomal RNA (rRNA).
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