scholarly journals The methamphetamine-induced RNA targetome of hnRNP H in Hnrnph1 mutants showing reduced dopamine release and behavior

2021 ◽  
Author(s):  
Qiu T Ruan ◽  
Michael A Rieger ◽  
William B Lynch ◽  
Jiayi Wu Cox ◽  
Jacob A Beierle ◽  
...  
Keyword(s):  
Dopamine Release ◽  
Rna Binding ◽  
Synaptic Proteins ◽  
Cross Linking ◽  
Regulate Gene Expression ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Frameshift Deletion ◽  
Behavioral Sensitivity ◽  
Nuclear Ribonucleoprotein ◽  
And Behavior

We previously identified Hnrnph1 (heterogeneous nuclear ribonucleoprotein H1) as a quantitative trait gene underlying reduced methamphetamine behavioral sensitivity. Mice with a heterozygous frameshift deletion in the first coding exon of Hnrnph1 showed reduced methamphetamine-induced dopamine release and behaviors. To inform the mechanism linking hnRNP H dysfunction with reduced methamphetamine-induced dopamine release and behavior, we surveyed the RNA targetome of hnRNP H via cross-linking immunoprecipitation coupled with RNA-sequencing in striatal tissue at baseline and at 30 min post-methamphetamine (2 mg/kg, i.p.). Methamphetamine induced opposite changes in RNA-binding targets of hnRNP H in Hnrnph1 mutants versus wild-types, including 3′UTR targets in mRNAs enriched for synaptic proteins involved in dopamine release and excitatory synaptic plasticity. Targetome, transcriptome, and spliceome analyses triangulated on a methamphetamine-induced upregulation of Cacna2d2 transcript and decreased 3′UTR usage in hyposensitive Hnrnph1 mutants. Our study identifies a dynamic methamphetamine-induced RNA targetome of hnRNP H that has the potential to rapidly regulate gene expression, synaptic transmission, plasticity, and behavior.

scholarly journals Heterogeneous Nuclear Ribonucleoprotein (hnRNP) E1 Binds to hnRNP A2 and Inhibits Translation of A2 Response Element mRNAs

2006 ◽  
Vol 17 (8) ◽  
pp. 3521-3533 ◽  
Author(s):  
Linda D. Kosturko ◽  
Michael J. Maggipinto ◽  
George Korza ◽  
Joo Won Lee ◽  
John H. Carson ◽  
...  
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
In Vitro Translation ◽  
Dependent Manner ◽  
Response Element ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Nuclear Ribonucleoprotein ◽  
Hnrnp E1

Heterogeneous nuclear ribonucleoprotein (hnRNP) A2 is a trans-acting RNA-binding protein that mediates trafficking of RNAs containing the cis-acting A2 response element (A2RE). Previous work has shown that A2RE RNAs are transported to myelin in oligodendrocytes and to dendrites in neurons. hnRNP E1 is an RNA-binding protein that regulates translation of specific mRNAs. Here, we show by yeast two-hybrid analysis, in vivo and in vitro coimmunoprecipitation, in vitro cross-linking, and fluorescence correlation spectroscopy that hnRNP E1 binds to hnRNP A2 and is recruited to A2RE RNA in an hnRNP A2-dependent manner. hnRNP E1 is colocalized with hnRNP A2 and A2RE mRNA in granules in dendrites of oligodendrocytes. Overexpression of hnRNP E1 or microinjection of exogenous hnRNP E1 in neural cells inhibits translation of A2RE mRNA, but not of non-A2RE RNA. Excess hnRNP E1 added to an in vitro translation system reduces translation efficiency of A2RE mRNA, but not of nonA2RE RNA, in an hnRNP A2-dependent manner. These results are consistent with a model where hnRNP E1 recruited to A2RE RNA granules by binding to hnRNP A2 inhibits translation of A2RE RNA during granule transport.

scholarly journals Physical and Functional Interaction between Heterochromatin Protein 1α and the RNA-binding Protein Heterogeneous Nuclear Ribonucleoprotein U

2009 ◽  
Vol 284 (41) ◽  
pp. 27974-27979 ◽  
Author(s):  
Maya Ameyar-Zazoua ◽  
Mouloud Souidi ◽  
Lauriane Fritsch ◽  
Philippe Robin ◽  
Audrey Thomas ◽  
...  
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Functional Interaction ◽  
Heterochromatin Protein ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Nuclear Ribonucleoprotein

scholarly journals The Heterogeneous Nuclear Ribonucleoprotein C Protein Tetramer Binds U1, U2, and U6 snRNAs through Its High Affinity RNA Binding Domain (the bZIP-like Motif)

1998 ◽  
Vol 273 (33) ◽  
pp. 21359-21367 ◽  
Author(s):  
Lillian Shahied-Milam ◽  
Syrus R. Soltaninassab ◽  
Gopakumar V. Iyer ◽  
Wallace M. LeStourgeon
Keyword(s):  
Rna Binding ◽  
Binding Domain ◽  
C Protein ◽  
High Affinity ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Rna Binding Domain ◽  
Nuclear Ribonucleoprotein

scholarly journals Heterogeneous nuclear ribonucleoprotein D0B is a sequence-specificDNA-binding protein

1999 ◽  
Vol 338 (2) ◽  
pp. 417-425 ◽  
Author(s):  
Mate TOLNAY ◽  
Lyudmila A. VERESHCHAGINA ◽  
George C. TSOKOS
Keyword(s):  
Dna Sequences ◽  
Rna Binding ◽  
Binding Protein ◽  
Double Helix ◽  
Physiological Role ◽  
Single Stranded Dna ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Double Stranded Dna ◽  
Nuclear Ribonucleoprotein

Complement receptor 2 (CR2) is important in the regulation of the B lymphocyte response; the regulation of its expression is therefore of central importance. We recently reported that a 42 kDa heterogeneous nuclear ribonucleoprotein (hnRNP) is involved in the transcriptional regulation of the human CR2 gene [Tolnay, Lambris and Tsokos (1997) J. Immunol. 159, 5492–5501]. We cloned the cDNA encoding this protein and found it to be identical with hnRNP D0B, a sequence-specific RNA-binding protein. By using a set of mutated oligonucleotides, we demonstrated that the recombinant hnRNP D0B displays sequence specificity for double-stranded oligonucleotide defined by the CR2 promoter. We conducted electrophoretic mobility-shift assays to estimate the apparent Kd of hnRNP D0B for the double-stranded DNA motif and found it to be 59 nM. Interestingly, hnRNP D0B displayed affinities of 28 and 18 nM for the sense and anti-sense strands of the CR2 promoter-defined oligonucleotide respectively. The significantly greater binding affinity of hnRNP D0B for single-stranded DNA than for double-stranded DNA suggests that the protein might melt the double helix. The intranuclear concentration of sequence-specific protein was estimated to be 250–400 nM, indicating that the protein binds to the CR2 promoter in vivo. Co-precipitation of a complex formed in vivo between hnRNP D0B and the TATA-binding protein demonstrates that hnRNP D0B interacts with the basal transcription apparatus. Our results suggest a new physiological role for hnRNP D0B that involves binding to double- and single-stranded DNA sequences in a specific manner and functioning as a transcription factor.

Both RNA-Binding Domains in Heterogeneous Nuclear Ribonucleoprotein A1 Contribute Toward Single-Stranded-RNA Binding

Biochemistry ◽  
1994 ◽  
Vol 33 (27) ◽  
pp. 8272-8281 ◽  
Author(s):  
Yousif Shamoo ◽  
Norzehan Abdul-Manan ◽  
Ann M. Patten ◽  
Janet K. Crawford ◽  
Matthew C. Pellegrini ◽  
...  
Keyword(s):  
Rna Binding ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Binding Domains ◽  
Rna Binding Domains ◽  
Nuclear Ribonucleoprotein

scholarly journals The mechanical regulation of RNA binding protein hnRNPC in the failing heart

2021 ◽  
Author(s):  
Fabiana Martino ◽  
Ana Rubina Perestrelo ◽  
Vaclav Hejret ◽  
Nandan Mysore Varadarajan ◽  
Helena Durikova ◽  
...  
Keyword(s):  
Active Site ◽  
Rna Binding ◽  
Hippo Pathway ◽  
Regulatory Protein ◽  
Rna Binding Protein ◽  
Ecm Remodeling ◽  
Biomechanical Stress ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Pathological Conditions ◽  
Nuclear Ribonucleoprotein

Cardiac pathologies are characterized by intense remodeling of the extracellular matrix (ECM) that eventually leads to heart failure. Cardiomyocytes respond to the ensuing biomechanical stress by re-expressing fetal contractile proteins via transcriptional and post-transcriptional processes, like alternative splicing (AS). Here, we demonstrate that the heterogeneous nuclear ribonucleoprotein C (hnRNPC) is upregulated and relocates to the sarcomeric Z-disk upon ECM pathological remodeling. We show that this is an active site of localized translation, where the ribonucleoprotein associates to the translation machinery. Alterations in hnRNPC expression and localization can be mechanically determined and affect the AS of numerous mRNAs involved in mechanotransduction and cardiovascular diseases, like Hippo pathway effector YAP1. We propose that cardiac ECM remodeling serves as a switch in RNA metabolism by impacting an associated regulatory protein of the spliceosome apparatus. These findings offer new insights on the mechanism of mRNAs homeostasis mechanoregulation in pathological conditions.

Classification and purification of proteins of heterogeneous nuclear ribonucleoprotein particles by RNA-binding specificities

1988 ◽  
Vol 8 (5) ◽  
pp. 2237-2241 ◽  
Author(s):  
M S Swanson ◽  
G Dreyfuss
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Binding Affinities ◽  
High Binding ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Hnrnp Proteins ◽  
Hnrnp C ◽  
One Step ◽  
Nuclear Ribonucleoprotein ◽  
Very High

Several proteins of heterogeneous nuclear ribonucleoprotein (hnRNP) particles display very high binding affinities for different ribonucleotide homopolymers. The specificity of some of these proteins at high salt concentrations and in the presence of heparin allows for their rapid one-step purification from HeLa nucleoplasm. We show that the hnRNP C proteins are poly(U)-binding proteins and compare their specificity to that of the previously described cytoplasmic poly(A)-binding protein. These findings provide a useful tool for the classification and purification of hnRNP proteins from various tissues and organisms and indicate that different hnRNP proteins have different RNA-binding specificities.

scholarly journals Heterogeneous nuclear ribonucleoprotein D0 contains transactivator and DNA-binding domains

2000 ◽  
Vol 348 (1) ◽  
pp. 151-158 ◽  
Author(s):  
Mate TOLNAY ◽  
Lajos BARANYI ◽  
George C. TSOKOS
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Dna Binding ◽  
Rna Binding ◽  
Dna Binding Domains ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Binding Domains ◽  
Double Stranded Dna ◽  
Nuclear Ribonucleoprotein

Heterogeneous nuclear ribonucleoprotein D0 (hnRNP D0) is an abundant, ubiquitous protein that binds RNA and DNA sequences specifically, and has been implicated in the transcriptional regulation of the human complement receptor 2 gene. We found that in vivo expression of hnRNP D0-GAL4 fusion proteins increased the transcriptional activity of a GAL4-driven reporter gene, providing direct proof that hnRNP D0 possesses a transactivator domain. We found, using truncated hnRNP D0 proteins fused to GAL4, that 29 amino acids in the N-terminal region are critical for transactivation. We established, using a series of recombinant truncated hnRNP D0 proteins, that the tandem RNA-binding domains alone were not able to bind double-stranded DNA. Nevertheless, 24 additional amino acids of the C-terminus imparted sequence-specific DNA binding. Experiments using peptide-specific antisera supported the importance of the 24-amino-acid region in DNA binding, and suggested the involvement of the 19-amino-acid alternative insert which is present in isoforms B and D. The N-terminus had an inhibitory effect on binding of hnRNP D0 to single-stranded, but not to double-stranded, DNA. Although both recombinant hnRNP D0B and D0D bound DNA, only the B isoform recognized DNA in vivo. We propose that the B isoform of hnRNP D0 functions in the nucleus as a DNA-binding transactivator and has distinct transactivator and DNA-binding domains.

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