scholarly journals Crystal structure of the human heterogeneous ribonucleoprotein A18 RNA-recognition motif

2017 ◽  
Vol 73 (4) ◽  
pp. 209-214 ◽  
Author(s):  
Katherine Coburn ◽  
Zephan Melville ◽  
Ehson Aligholizadeh ◽  
Braden M. Roth ◽  
Kristen M. Varney ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Recognition Motif ◽  
Rna Recognition ◽  
Hnrnp A1 ◽  
Structure Based Drug Design ◽  
Recognition Motif ◽  
Protein Nucleic Acid ◽  
Nucleic Acid Interactions

The heterogeneous ribonucleoprotein A18 (hnRNP A18) is upregulated in hypoxic regions of various solid tumors and promotes tumor growthviathe coordination of mRNA transcripts associated with pro-survival genes. Thus, hnRNP A18 represents an important therapeutic target in tumor cells. Presented here is the first X-ray crystal structure to be reported for the RNA-recognition motif of hnRNP A18. By comparing this structure with those of homologous RNA-binding proteins (i.e.hnRNP A1), three residues on one face of an antiparallel β-sheet (Arg48, Phe50 and Phe52) and one residue in an unstructured loop (Arg41) were identified as likely to be involved in protein–nucleic acid interactions. This structure helps to serve as a foundation for biophysical studies of this RNA-binding protein and structure-based drug-design efforts for targeting hnRNP A18 in cancer, such as malignant melanoma, where hnRNP A18 levels are elevated and contribute to disease progression.

scholarly journals CUS2, a Yeast Homolog of Human Tat-SF1, Rescues Function of Misfolded U2 through an Unusual RNA Recognition Motif

1998 ◽  
Vol 18 (9) ◽  
pp. 5000-5009 ◽  
Author(s):  
Dong Yan ◽  
Rhonda Perriman ◽  
Haller Igel ◽  
Kenneth J. Howe ◽  
Megan Neville ◽  
...  
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Normal Activity ◽  
Binding Activity ◽  
Rna Recognition Motif ◽  
Rna Recognition ◽  
Recognition Motif ◽  
Yeast Homolog

ABSTRACT A screen for suppressors of a U2 snRNA mutation identified CUS2, an atypical member of the RNA recognition motif (RRM) family of RNA binding proteins. CUS2 protein is associated with U2 RNA in splicing extracts and interacts with PRP11, a subunit of the conserved splicing factor SF3a. Absence of CUS2 renders certain U2 RNA folding mutants lethal, arguing that a normal activity of CUS2 is to help refold U2 into a structure favorable for its binding to SF3b and SF3a prior to spliceosome assembly. Both CUS2 function in vivo and the in vitro RNA binding activity of CUS2 are disrupted by mutation of the first RRM, suggesting that rescue of misfolded U2 involves the direct binding of CUS2. Human Tat-SF1, reported to stimulate Tat-specific, transactivating region-dependent human immunodeficiency virus transcription in vitro, is structurally similar to CUS2. Anti-Tat-SF1 antibodies coimmunoprecipitate SF3a66 (SAP62), the human homolog of PRP11, suggesting that Tat-SF1 has a parallel function in splicing in human cells.

scholarly journals Involvement of a tissue-specific RNA recognition motif protein in Drosophila spermatogenesis.

1997 ◽  
Vol 17 (5) ◽  
pp. 2708-2715 ◽  
Author(s):  
S R Haynes ◽  
M T Cooper ◽  
S Pype ◽  
D T Stolow
Keyword(s):  
Posttranscriptional Regulation ◽  
Rna Binding ◽  
Protein Gene ◽  
Germ Line ◽  
Rna Binding Proteins ◽  
Regulation Of Gene Expression ◽  
Rna Recognition Motif ◽  
Rna Recognition ◽  
Two Dimensional Gel Electrophoresis ◽  
Recognition Motif

RNA binding proteins mediate posttranscriptional regulation of gene expression via their roles in nuclear and cytoplasmic mRNA metabolism. Many of the proteins involved in these processes have a common RNA binding domain, the RNA recognition motif (RRM). We have characterized the Testis-specific RRM protein gene (Tsr), which plays an important role in spermatogenesis in Drosophila melanogaster. Disruption of Tsr led to a dramatic reduction in male fertility due to the production of spermatids with abnormalities in mitochondrial morphogenesis. Tsr is located on the third chromosome at 87F, adjacent to the nuclear pre-mRNA binding protein gene Hrb87F. A 1.7-kb Tsr transcript was expressed exclusively in the male germ line. It encoded a protein containing two RRMs similar to those found in HRB87F as well as a unique C-terminal domain. TSR protein was located in the cytoplasm of spermatocytes and young spermatids but was absent from mature sperm. The cellular proteins expressed in premeiotic primary spermatocytes from Tsr mutant and wild-type males were assessed by two-dimensional gel electrophoresis. Lack of TSR resulted in the premature expression of a few proteins prior to meiosis; this was abolished by a transgenic copy of Tsr. These data demonstrate that TSR negatively regulated the expression of some testis proteins and, in combination with its expression pattern and subcellular localization, suggest that TSR regulates the stability or translatability of some mRNAs during spermatogenesis.

scholarly journals A Negative Coregulator for the Human ER

2002 ◽  
Vol 16 (3) ◽  
pp. 459-468 ◽  
Author(s):  
John D. Norris ◽  
Daju Fan ◽  
Andrea Sherk ◽  
Donald P. McDonnell
Keyword(s):  
Transcriptional Activity ◽  
Cellular Proliferation ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Partial Agonist ◽  
Rna Recognition Motif ◽  
Rna Recognition ◽  
Agonist Activity ◽  
Partial Agonist Activity ◽  
Recognition Motif

Abstract ERα is a ligand-activated transcription factor and a key regulator of the processes involved in cellular proliferation and differentiation. In addition, aberrant ERα activity is linked to several pathological conditions including breast cancer. A complex network of coregulatory proteins is largely believed to determine the transcriptional activity of ERα. We report here the isolation of a protein, denoted RTA for repressor of tamoxifen transcriptional activity, which contains an RNA recognition motif and interacts with the receptor N-terminal activation domain. RTA interacts with RNA in vitro, and its overexpression inhibits the partial agonist activity manifest by the antiestrogen tamoxifen while minimally affecting E2-activated transcription. Mutation of the RNA recognition motif alters RNA binding specificity and results in a dominant negative form of RTA that leads to derepression of ERα transcriptional activity, allowing all classes of antiestrogens to manifest partial agonist activity and enhancing agonist efficacy. These findings suggest a role for RNA binding proteins as coregulatory factors of the nuclear receptor family and reveal a novel mechanism by which antiestrogens can manifest agonist activities in some tissues.

scholarly journals Crystal structure of human Acinus RNA recognition motif domain

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5163 ◽  
Author(s):  
Humberto Fernandes ◽  
Honorata Czapinska ◽  
Katarzyna Grudziaz ◽  
Janusz M. Bujnicki ◽  
Martyna Nowacka
Keyword(s):  
Crystal Structure ◽  
Rna Binding ◽  
Chromatin Condensation ◽  
Rna Recognition Motif ◽  
Target Sequence ◽  
Rna Recognition ◽  
Recognition Motif ◽  
Rrm Domain ◽  
Α Helix ◽  
Β Sheet

Acinus is an abundant nuclear protein involved in apoptosis and splicing. It has been implicated in inducing apoptotic chromatin condensation and DNA fragmentation during programmed cell death. Acinus undergoes activation by proteolytic cleavage that produces a truncated p17 form that comprises only the RNA recognition motif (RRM) domain. We have determined the crystal structure of the human Acinus RRM domain (AcRRM) at 1.65 Å resolution. It shows a classical four-stranded antiparallel β-sheet fold with two flanking α-helices and an additional, non-classical α-helix at the C-terminus, which harbors the caspase-3 target sequence that is cleaved during Acinus activation. In the structure, the C-terminal α-helix partially occludes the potential ligand binding surface of the β-sheet and hypothetically shields it from non-sequence specific interactions with RNA. Based on the comparison with other RRM-RNA complex structures, it is likely that the C-terminal α-helix changes its conformation with respect to the RRM core in order to enable RNA binding by Acinus.

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