The acidic domain of hnRNPQ (NSAP1) has structural similarity to Barstar and binds to Apobec1

Quaresma, Alexandre J.C.; Oyama, Sílvia Maria Ribeiro; Barbosa, J.A.R.G.; Kobarg, Jörg

doi:10.1016/j.bbrc.2006.09.044

Cited by 14 publications

(21 citation statements)

References 35 publications

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“…long 3’UTR), but had no effect on expression level of HLA-A*11, an allotype associated with only the short form. Syncrip (alias HNRNPQ1, Nsap1) is a ubiquitously expressed, cytoplasmic isoform of the RBP HNRNPQ (18–20), and is known to regulate splicing (21–24), editing (25–27), transport (28–32), translation (33–42), and stability (43–48) of mRNA. Syncrip binding sites are enriched in two core consensus sequences (AYAAYY and UAUYRR; Y=C/U and R=A/G) (29) as well as AU rich elements (ARE)(25).…”

Section: Discussionmentioning

confidence: 99%

Posttranscriptional Regulation of HLA-A Protein Expression by Alternative Polyadenylation Signals Involving the RNA-Binding Protein Syncrip

Kulkarni

Ramsuran

Ručević

et al. 2017

The Journal of Immunology

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Genomic variation in the untranslated region (UTR) has been shown to influence human leukocyte antigen (HLA) class I expression level, and associate with disease outcomes. Sequencing of the 3’UTR of common HLA-A alleles indicated the presence of two polyadenylation signals (PAS). The proximal PAS is conserved, whereas the distal PAS is disrupted within certain alleles by sequence variants. Using 3’ rapid amplification of cDNA ends (3’RACE), we confirmed expression of two distinct forms of the HLA-A 3’UTR based on use of either the proximal or the distal PAS, which differ in length by 100 base pairs. Specific HLA-A alleles varied in the usage of the proximal vs. distal PAS, with some alleles using only the proximal, and others using both the proximal and distal PAS to differing degrees. We show that the short and the long 3’UTR produced similar mRNA expression levels. However, the long 3’UTR conferred lower luciferase activity as compared to the short form, indicating translation inhibition of the long 3’UTR. RNA affinity pull down followed by mass spectrometry (MS) analysis as well as RNA co-immunoprecipitation indicated differential binding of Syncrip to the long vs. short 3’UTR. Depletion of Syncrip by siRNA increased surface expression of an HLA-A allotype that uses primarily the long 3’UTR, whereas an allotype expressing only the short form was unaffected. Further, specific blocking of the proximal 3’UTR reduced surface expression without decreasing mRNA expression. These data demonstrate HLA-A allele-specific variation in PAS usage, which modulates their cell surface expression post-transcriptionally.

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Section: Discussionmentioning

confidence: 99%

Posttranscriptional Regulation of HLA-A Protein Expression by Alternative Polyadenylation Signals Involving the RNA-Binding Protein Syncrip

Kulkarni

Ramsuran

Ručević

et al. 2017

The Journal of Immunology

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“…Therefore, hnRNPQ2, hnRNP4, or both may be involved in other APOBEC1-dependent functions. The other hnRNPQ isoforms have at least one domain required for association with APOBEC1, namely an N-terminal acidic domain (23) or C-terminal domain (24); therefore, any of these isoforms may associate with APOBEC1 to regulate its function.…”

Section: Discussionmentioning

confidence: 99%

The RNA-editing Enzyme APOBEC1 Requires Heterogeneous Nuclear Ribonucleoprotein Q Isoform 6 for Efficient Interaction with Interleukin-8 mRNA

Shimizu

Nishitsuji

Marusawa

et al. 2014

Journal of Biological Chemistry

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Background: APOBEC1 stabilizes target mRNAs by suppressing nonsense-or AU-rich element-mediated decay; however, the mechanisms regulating target selection are unknown. Results: In the presence of hnRNPQ isoform 6, APOBEC1 stabilizes interleukin-8 mRNA independently of APOBEC1 complementation factor. Conclusion: APOBEC1 utilizes a complementing protein to select target mRNAs. Significance: These data shed light on the selective regulation of APOBEC1 target genes.

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“…In particular, the RRMs of A1CF show strong homology to the RRMs found in the hnRNPs. APOBEC1 also can interact with more than one isoform of hnRNP Q, which shows almost 50% identity with A1CF (19). Members of the hnRNP protein family are involved in multiple aspects of nucleic acid metabolism and show distinct binding preferences for nucleic acids and proteins.…”

Section: Significancementioning

confidence: 99%

“…The specificity of the APOBEC1 RNA-editing activity is determined by its cofactor, APOBEC1 complementation factor/ APOBEC complementation factor (A1CF/ACF), a 64-kDa RNAbinding protein containing three distinct RNA-recognition motifs (RRMs) (19)(20)(21)(22)(23), which specifically targets a single C within a transcript of ∼14,000 bases. A conserved motif of 11 nucleotides (referred to as the "mooring sequence"), located four to six nucleotides downstream of the edited base, is critical for A1CF binding and RNA editing (24,25).…”

mentioning

confidence: 99%

Identification of DNA cleavage- and recombination-specific hnRNP cofactors for activation-induced cytidine deaminase

Begum

Mondal

et al. 2015

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

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Activation-induced cytidine deaminase (AID) is essential for antibody class switch recombination (CSR) and somatic hypermutation (SHM). AID originally was postulated to function as an RNAediting enzyme, based on its strong homology with apolipoprotein B mRNA-editing enzyme, catalytic polypeptide 1 (APOBEC1), the enzyme that edits apolipoprotein B-100 mRNA in the presence of the APOBEC cofactor APOBEC1 complementation factor/APOBEC complementation factor (A1CF/ACF). Because A1CF is structurally similar to heterogeneous nuclear ribonucleoproteins (hnRNPs), we investigated the involvement of several well-known hnRNPs in AID function by using siRNA knockdown and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9-mediated disruption. We found that hnRNP K deficiency inhibited DNA cleavage and thereby induced both CSR and SHM, whereas hnRNP L deficiency inhibited only CSR and somewhat enhanced SHM. Interestingly, both hnRNPs exhibited RNA-dependent interactions with AID, and mutant forms of these proteins containing deletions in the RNA-recognition motif failed to rescue CSR. Thus, our study suggests that hnRNP K and hnRNP L may serve as A1CF-like cofactors in AID-mediated CSR and SHM.class switch recombination | somatic hypermutation | activation-induced cytidine deaminase | B cell | IgH A ntigen-stimulated mature B cells express activation-induced cytidine deaminase (AID), an essential enzyme for somatic hypermutation (SHM) and class switch recombination (CSR) at the Ig locus (1, 2). AID induces DNA breaks at the variable (V) and switch (S) regions during SHM and CSR, respectively. Most of the mutations produced during SHM are introduced by errorprone DNA synthesis during single-strand break (SSB) repair (3, 4). In contrast, CSR requires the conversion of SSBs to doublestrand breaks (DSBs), followed by recombination between two DSB ends located in the donor and acceptor S regions (5, 6). The entire process of CSR is accomplished through elaborate DNArepair processes involving S-S synapse formation and end-joining.The mechanism by which AID functions differently in DNA cleavage and recombination at different loci remains unclear. Functional studies of a large number of AID mutants revealed that the N-terminal AID mutations impair SHM and CSR, indicating that the AID N terminus, which also possesses a bipartite nuclear-localization signal, is required for DNA cleavage in both SHM and CSR (7-9). On the other hand, C-terminal AID mutations suppressed the recombination activity of CSR but had no effect on SHM, indicating that the C terminus of AID, which contains a nuclear-export signal, is required for the recombination activity associated specifically with CSR (7, 9, 10). Indeed, recent studies showed that defects in the AID C terminus compromise DNA end-joining and S-S synapse formation without perturbing DNA breakage at either the V or S region (11, 12), also suggesting a specific role for the AID C terminus in the recombination step of CSR. Given AID's small size (198 resi...

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The acidic domain of hnRNPQ (NSAP1) has structural similarity to Barstar and binds to Apobec1

Cited by 14 publications

References 35 publications

Posttranscriptional Regulation of HLA-A Protein Expression by Alternative Polyadenylation Signals Involving the RNA-Binding Protein Syncrip

Posttranscriptional Regulation of HLA-A Protein Expression by Alternative Polyadenylation Signals Involving the RNA-Binding Protein Syncrip

The RNA-editing Enzyme APOBEC1 Requires Heterogeneous Nuclear Ribonucleoprotein Q Isoform 6 for Efficient Interaction with Interleukin-8 mRNA

Identification of DNA cleavage- and recombination-specific hnRNP cofactors for activation-induced cytidine deaminase

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