TCEAL1 Human
Description
TCEAL1 Human: Genomic and Molecular Overview
TCEAL1 (transcription elongation factor A-like 1) is an X-linked gene located at chromosomal band Xq22.1, encoding a 21-kDa nuclear phosphoprotein critical for transcriptional regulation . As a member of the TCEAL family, it shares structural homology with transcription elongation factor A (TEF A/SII) and contains three functional domains:
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Arginine/Serine (RS) domain: Involved in RNA polymerase II interactions.
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Zinc-finger-like (ZnF-L) domain: Potential role in DNA binding or protein interactions.
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Helix-turn-helix (HTH) domain: May mediate transcriptional activation .
TCEAL1 in Neurodevelopmental Disorders
TCEAL1 mutations are associated with a distinct X-linked dominant neurodevelopmental syndrome characterized by:
Recent studies highlight truncating variants (e.g., frameshift, nonsense mutations) as the primary pathogenic mechanism, particularly in the ZnF-L and HTH domains . Males with hemizygous mutations exhibit more severe phenotypes, while females with heterozygous mutations show milder symptoms due to X-inactivation patterns .
Variant-Phenotype Correlations
Studies using trio exome/genome sequencing identified truncating variants in TCEAL1 as the driver of disease:
Molecular Mechanisms
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Transcriptional Regulation: TCEAL1 interacts with transcriptional machinery via its RS and ZnF-L domains, modulating promoter activity in a context-dependent manner .
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Nonsense-Mediated Decay (NMD) Escape: Variants in the terminal exon evade NMD, leading to truncated but partially functional proteins .
Diagnostic and Therapeutic Advances
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Xq22.2 Deletions: Larger deletions encompassing TCEAL1 and adjacent genes (e.g., TCEAL3, TCEAL4) correlate with broader neurodevelopmental phenotypes .
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Adult-Onset Features: Emerging data highlight metabolic and endocrine abnormalities (e.g., hyperinsulinemia, hyperandrogenemia) in adult females, necessitating multidisciplinary care .
Open Questions
Product Specs
Q&A
Basic Research Questions
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What experimental approaches are used to identify TCEAL1-associated neurodevelopmental disorders?
Trio exome sequencing and chromosomal microarray analyses are standard for detecting TCEAL1 variants. Key steps include:-
Variant prioritization: Focus on de novo truncating variants (e.g., frameshift, nonsense) in the single coding exon of TCEAL1 .
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Phenotype correlation: Assess clinical features (hypotonia, intellectual disability, dysmorphic facial features) against variant type and location (e.g., variants in ZnF-L or HTH domains correlate with severe phenotypes) .
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Functional validation: Use RNA analysis to confirm nonsense-mediated decay (NMD) escape for truncating variants in exon 3 .
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How does TCEAL1 influence transcription regulation?
TCEAL1 stabilizes RNA Polymerase II (RNAPII) on chromatin through interactions with USP11 and USP7, forming a trimeric complex that maintains transcription elongation. Methodological insights:
Advanced Research Questions
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How do TCEAL1 variant types (truncating vs. missense) differentially impact molecular function?
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What explains contradictions in phenotype-genotype correlations for TCEAL1 variants?
Discrepancies arise from:-
X-inactivation skewing: Females with heterozygous truncating variants show variable symptom severity due to random X-inactivation (e.g., 77% skewing in Individual 1) .
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Allelic heterogeneity: A maternally inherited missense variant (p.Arg101Trp) caused spasticity in a male without classical syndromic features, suggesting context-dependent effects .
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Resolution strategy: Combine long-read sequencing to phase variants and single-cell RNA-seq to assess allele-specific expression in patient-derived neurons .
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How does TCEAL1 integrate into species-specific transcriptional networks?
Comparative co-expression analyses reveal:-
Human-specific links: TCEAL1 gained >2 standard deviations more regulatory interactions with genes like ZFHX1B and ZNF295 compared to chimpanzees, implicating it in human neuroevolution .
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Methodology: Use cross-species weighted gene co-expression network analysis (WGCNA) to identify conserved vs. divergent modules .
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Methodological Guidance
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What in vitro models are optimal for studying TCEAL1 loss-of-function?
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How to resolve conflicting data on TCEAL1’s role in cancer vs. neurodevelopment?
Product Science Overview
Transcription Elongation Factor A (SII)-Like 1, also known as TCEANC, is a protein-coding gene that plays a crucial role in the transcription process. This protein is involved in the elongation phase of transcription, which is a critical step in the synthesis of RNA from a DNA template. The human recombinant form of this protein is used in various research and therapeutic applications.
The TCEANC gene encodes the Transcription Elongation Factor A (SII)-Like 1 protein. This gene is located on chromosome 1 and is composed of multiple exons that are transcribed into mRNA. The protein itself consists of several domains that are essential for its function in transcription elongation. These domains include the N-terminal and central domains, which are involved in the interaction with RNA polymerase II and other transcription factors .
The primary function of Transcription Elongation Factor A (SII)-Like 1 is to facilitate the elongation phase of transcription by RNA polymerase II. During transcription, RNA polymerase II can encounter obstacles that cause it to pause or backtrack. TCEANC helps to resolve these issues by inducing cleavage of the nascent RNA, allowing transcription to resume from the new 3’-terminus . This activity is crucial for the efficient and accurate synthesis of RNA molecules.
Transcription Elongation Factor A (SII)-Like 1 is essential for the proper regulation of gene expression. By ensuring the smooth progression of RNA polymerase II during transcription, TCEANC plays a vital role in the expression of genes involved in various cellular processes. Dysregulation of this protein can lead to transcriptional errors and has been associated with certain diseases, including infantile myofibromatosis .
The human recombinant form of Transcription Elongation Factor A (SII)-Like 1 is used in research to study the mechanisms of transcription elongation and its regulation. It is also utilized in therapeutic applications to investigate potential treatments for diseases caused by transcriptional dysregulation. The availability of recombinant TCEANC allows researchers to conduct experiments with a consistent and reliable source of the protein.
