hnRNP A2/B1 binds specifically to single stranded vertebrate telomeric repeat TTAGGG<sub>n</sub>

McKay, Sonia; Cooke, Howard J.

doi:10.1093/nar/20.24.6461

Cited by 126 publications

(91 citation statements)

References 16 publications

(14 reference statements)

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“…hnRNP A2 binds the telomeric sequence TTAGGG (24,25,43), which bears no relationship to the A2RE sequence and is therefore unlikely to mimic the A2RE binding detected in this study. Because heparin was not used in the studies with telomeric DNA, it is possible that the TTAGGG sequence binds with an atypically high affinity to the nonspecific site; alternatively, it may interact with a specific site on hnRNP A2 other than the one described here.…”

Section: Binding Of Point Mutants Of A2re11-earliermentioning

confidence: 67%

“…In addition to being a major component of core particles (23), hnRNP A2 binds a telomeric sequence (24,25,43) and a small RNA segment known to be necessary and sufficient for transport of the message encoding myelin basic protein in the cytoplasm of oligodendrocytes, the A2RE (26 -28). The binding of hnRNP A2 to A2RE has been shown, by mutational and antisense approaches, to be essential for cytoplasmic RNA trafficking in oligodendrocytes (29).…”

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confidence: 99%

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Binding of an RNA Trafficking Response Element to Heterogeneous Nuclear Ribonucleoproteins A1 and A2

Shan

Moran-Jones

Munro

et al. 2000

Journal of Biological Chemistry

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Heterogeneous nuclear ribonucleoprotein (hnRNP) A2 binds a 21-nucleotide myelin basic protein mRNA response element, the A2RE, and A2RE-like sequences in other localized mRNAs, and is a trans-acting factor in oligodendrocyte cytoplasmic RNA trafficking. Recombinant human hnRNPs A1 and A2 were used in a biosensor to explore interactions with A2RE and the cognate oligodeoxyribonucleotide. Both proteins have a single site that bound oligonucleotides with markedly different sequences but did not bind in the presence of heparin. Both also possess a second, specific site that bound only A2RE and was unaffected by heparin. hnRNP A2 bound A2RE in the latter site with a K d near 50 nM, whereas the K d for hnRNP A1 was above 10 M. UV cross-linking assays led to a similar conclusion. Mutant A2RE sequences, that in earlier qualitative studies appeared not to bind hnRNP A2 or support RNA trafficking in oligodendrocytes, had dissociation constants above 5 M for this protein. The two concatenated RNA recognition motifs (RRMs), but not the individual RRMs, mimicked the binding behavior of hnRNP A2. These data highlight the specificity of the interaction of A2RE with these hnRNPs and suggest that the sequence-specific A2RE-binding site on hnRNP A2 is formed by both RRMs acting in cis.The family of more than 20 heterogeneous nuclear ribonucleoproteins (hnRNPs) 1 appears to play diverse roles in the post-transcriptional processing of hnRNA and subsequent packaging, transport, and translation of mRNA (1-4). hnRNPs A1, A2, B1, B2, C1, and C2 are the major components of 40S "core particles," studied primarily in HeLa cells, which are thought to package nascent ssRNA in the nucleus in a histonelike fashion (5-10). The hnRNP A/B proteins have a modular structure with two N-terminal RNA recognition motifs (RRMs) followed by a glycine-rich region ( Fig. 1) (11). The three-dimensional structures of the tandem RRMs of hnRNP A1, which are assumed to be the principal mediators of the RNA-protein interactions, have been determined (12, 13). Although the three-dimensional structures of other hnRNPs of the A/B family have not been determined, their RRMs share sufficient sequence identity with those of hnRNP A1 to suggest that they share the same tertiary fold: a four-stranded antiparallel ␤-sheet flanked by two helices. This module adopts a comparable fold in the RRMs of more distantly related proteins, such as U1A (14 -17).Although a number of the hnRNPs have a general role in intranuclear packaging of RNA, some also manifest sequencespecific binding (1, 4, 18 -22). In addition to being a major component of core particles (23), hnRNP A2 binds a telomeric sequence (24, 25, 43) and a small RNA segment known to be necessary and sufficient for transport of the message encoding myelin basic protein in the cytoplasm of oligodendrocytes, the A2RE (26 -28). The binding of hnRNP A2 to A2RE has been shown, by mutational and antisense approaches, to be essential for cytoplasmic RNA trafficking in oligodendrocytes (29).Although hnRNP A2 has been shown to ...

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Section: Binding Of Point Mutants Of A2re11-earliermentioning

confidence: 67%

mentioning

confidence: 99%

Binding of an RNA Trafficking Response Element to Heterogeneous Nuclear Ribonucleoproteins A1 and A2

Shan

Moran-Jones

Munro

et al. 2000

Journal of Biological Chemistry

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“…Other groups of RNA-binding proteins are capable of binding directly to single-stranded telomeric DNA. For example, hnRNP A1 was shown to bind single-stranded telomeric DNA and telomerase RNA [35]. Depletion of hnRNP A1 expression causes short telomeres and reduces telomerase activity [46,47].…”

Section: Discussionmentioning

confidence: 99%

“…Because the single-stranded character of RNA and single-stranded DNA is similar, RNA-binding proteins tend to bind single-stranded DNA. For example, several human hnRNPs (heterogeneous nuclear ribonucleoproteins) were shown to bind both RNA and singlestranded telomeric DNA [35,36]. We then tested whether Imp4p could also bind to single-stranded telomeric DNA.…”

Section: Specific Binding Of Imp4p To Single-stranded Telomeric Dnamentioning

confidence: 99%

The U3 small nucleolar ribonucleoprotein component Imp4p is a telomeric DNA-binding protein

Hsieh¹,

Tu²,

Lee³

et al. 2007

Biochemical Journal

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Imp4p is a component of U3 snoRNP (small nucleolar ribonucleoprotein) involved in the maturation of 18S rRNA. We have shown that Imp4p interacts with Cdc13p, a single-stranded telomere-binding protein involved in telomere maintenance. To understand the role of Imp4p in telomeres, we purified recombinant Imp4p protein and tested its binding activity towards telomeric DNA using electrophoretic mobility-shift assays. Our results showed that Imp4p bound specifically to single-stranded telomeric DNA in vitro. The interaction of Imp4p to telomeres in vivo was also demonstrated by chromatin immunoprecipitation experiments. Significantly, the binding of Imp4p to telomeres was not limited to yeast proteins, since the hImp4 (human Imp4) also bound to vertebrate single-stranded telomeric DNA. Thus we conclude that Imp4p is a novel telomeric DNA-binding protein that, in addition to its role in rRNA processing, might participate in telomere function.

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“…Another group of proteins, ST-2 from Trypanosoma [8], qTBP42 from rat [9], human replication factor C [10], and murine STBP [11] and A1/UP1 [12], also bind to the single-stranded G-rich telomeric motif, although their function has not been fully ascertained. The last of these, however, is the first ssDNA-binding protein shown to be directly involved in mammalian telomere biogenesis, suggesting a possible mechanism by which telomere length can be modulated [13].…”

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confidence: 99%

A chicken hnRNP of the A/B family recognizes the single‐stranded d(CCCTAA)_n telomeric repeated motif

Marsich¹,

Bandiera²,

Tell³

et al. 2001

European Journal of Biochemistry

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With the aim of identifying proteins able to interact with the C-rich single-stranded telomeric repeated motif, three nuclear polypeptides, CBNPa, CBNPb and CBNPg, with apparent mobilities in SDS/PAGE of 38, 44 and 55 kDa, respectively, were isolated from mature chicken erythrocytes by affinity chromatography. In situ UV-cross-linking experiments demonstrated that CBNPa and CBNPg interact directly with the telomeric d(CCCTAA) n repeat, whereas CBNPb does not. Moreover, they provided information on the protein components responsible for each electrophoretic mobility-shift assay signal. Ion spray and matrix-assisted laser desorption ionization MS allowed us to identify CBNPa with single-stranded D-box-binding factor (ssDBF), a protein previously characterized as a transcription factor belonging to the A/B family of heterogeneous nuclear ribonucleoproteins, and CBNPb with an isoform of this protein containing an extra exon. Similarly, CBNPg was shown to be probably the chicken homolog of hnRNP K, a ribonuclear protein able to bind to polyC oligonucleotides. The relation of CBNPa (i.e. ssDBF), CBNPb and CBNPg to a number of similar proteins in the protein and nucleotide sequence databank is discussed. A rather diversified spectrum of functional roles has been assigned to some of these proteins despite the strong sequence homology among them.Keywords: heterogeneous ribonucleoproteins (hnRNPs); nuclear proteins; ssDNA recognition; telomeric C-rich motif.Since the discovery of the special features of repetitive DNA which constitutes the majority of telomeres of eukaryotic organisms, and of its specific replication machinery, considerable attention has also been directed to identifying and characterizing nuclear proteins that specifically bind to this DNA, in the normal Watson±Crick duplex form, as well as to the protruding single-stranded G-rich 3 H overhang at the telomere terminus. Many proteins such as TRF1 and TRF2 that bind to duplex telomeric DNA in mammalian cells [1] and Rap1p in yeast [2] have been reported to be involved in telomere length maintenance and regulation of telomerase activity. In unicellular organisms, several proteins, such as ab protein from Oxytricha , also bind to the single-stranded G-rich telomeric motif, although their function has not been fully ascertained. The last of these, however, is the first ssDNA-binding protein shown to be directly involved in mammalian telomere biogenesis, suggesting a possible mechanism by which telomere length can be modulated [13]. Much less attention has been given to identifying nuclear components able to recognize the complementary single-stranded C-rich DNA repeat. Interestingly, a protein from Trypanosoma, ST-1, binds to the telomeric double-stranded repeat as well as to its singlestranded C-rich component [14]. In vertebrates, the nuclear protein from rat hepatocytes, qTBP42, has been shown to recognize each of the single-stranded forms of the telomeric repeat [9]. Several proteins that interact with polypyrimidine ssDNA have been described. They includ...

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hnRNP A2/B1 binds specifically to single stranded vertebrate telomeric repeat TTAGGG_n

Cited by 126 publications

References 16 publications

Binding of an RNA Trafficking Response Element to Heterogeneous Nuclear Ribonucleoproteins A1 and A2

Binding of an RNA Trafficking Response Element to Heterogeneous Nuclear Ribonucleoproteins A1 and A2

The U3 small nucleolar ribonucleoprotein component Imp4p is a telomeric DNA-binding protein

A chicken hnRNP of the A/B family recognizes the single‐stranded d(CCCTAA)_n telomeric repeated motif

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hnRNP A2/B1 binds specifically to single stranded vertebrate telomeric repeat TTAGGGn

Cited by 126 publications

References 16 publications

Binding of an RNA Trafficking Response Element to Heterogeneous Nuclear Ribonucleoproteins A1 and A2

Binding of an RNA Trafficking Response Element to Heterogeneous Nuclear Ribonucleoproteins A1 and A2

The U3 small nucleolar ribonucleoprotein component Imp4p is a telomeric DNA-binding protein

A chicken hnRNP of the A/B family recognizes the single‐stranded d(CCCTAA)n telomeric repeated motif

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hnRNP A2/B1 binds specifically to single stranded vertebrate telomeric repeat TTAGGG_n

A chicken hnRNP of the A/B family recognizes the single‐stranded d(CCCTAA)_n telomeric repeated motif