scholarly journals The Coactivator activator CoAA regulates PEA3 group member transcriptional activity

2011 ◽  
Vol 439 (3) ◽  
pp. 469-477 ◽  
Author(s):  
Kathye Verreman ◽  
Jean-Luc Baert ◽  
Alexis Verger ◽  
Hervé Drobecq ◽  
Elisabeth Ferreira ◽  
...  
Keyword(s):  
Transcriptional Activity ◽  
Human Cancer ◽  
Rna Recognition ◽  
Rna Recognition Motifs ◽  
Human Cancer Cells ◽  
Important Regulator ◽  
Group Members ◽  
Recognition Motifs ◽  
Nuclear Ribonucleoprotein ◽  
Group Member

The PEA3 (polyoma enhancer activator 3) group members [ERM (ETS-related molecule), ER81 (ETS-related 81) and PEA3] of the Ets transcription factor family are involved in migration and dissemination processes during organogenesis and cancer development. In the present study, we report that the hnRNP (heterogeneous nuclear ribonucleoprotein)-like protein CoAA (Coactivator activator) interacts with the PEA3 group members and modulates their transcriptional activity. We also demonstrate that the CoAA YQ domain, containing tyrosine/glutamine-rich hexapeptide repeats, is necessary for the interaction, whereas the two N-terminal RRMs (RNA recognition motifs) of CoAA are required to enhance transcriptional activity. Finally, we show that CoAA is involved in the migration-enhancing action of PEA3 on MCF7 human cancer cells, suggesting that CoAA might be an important regulator of PEA3 group member activity during metastasis.

scholarly journals Differential Conformational Dynamics Encoded by the Linker between Quasi RNA Recognition Motifs of Heterogeneous Nuclear Ribonucleoprotein H

2018 ◽  
Vol 140 (37) ◽  
pp. 11661-11673 ◽  
Author(s):  
Srinivasa R. Penumutchu ◽  
Liang-Yuan Chiu ◽  
Jennifer L. Meagher ◽  
Alexandar L. Hansen ◽  
Jeanne A. Stuckey ◽  
...  
Keyword(s):  
Conformational Dynamics ◽  
Rna Recognition ◽  
Rna Recognition Motifs ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Recognition Motifs ◽  
Nuclear Ribonucleoprotein

scholarly journals Minimal functional domains of paralogues hnRNP L and hnRNP LL exhibit mechanistic differences in exonic splicing repression

2013 ◽  
Vol 453 (2) ◽  
pp. 271-279 ◽  
Author(s):  
Ganesh Shankarling ◽  
Kristen W. Lynch
Keyword(s):  
Sequence Similarity ◽  
Expression Patterns ◽  
Rna Recognition ◽  
High Sequence Similarity ◽  
Rna Recognition Motifs ◽  
Hnrnp Proteins ◽  
Functional Consequences ◽  
Recognition Motifs ◽  
Nuclear Ribonucleoprotein ◽  
Specific Control

Understanding functional distinctions between related splicing regulatory proteins is critical to deciphering tissue-specific control of alternative splicing. The hnRNP (heterogeneous nuclear ribonucleoprotein) L and hnRNP LL (hnRNP L-like) proteins are paralogues that have overlapping, but distinct, expression patterns and functional consequences. These two proteins share high sequence similarity in their RRMs (RNA-recognition motifs), but diverge in regions outside of the RRMs. In the present study, we use an MS2-tethering assay to delineate the minimal domains of hnRNP L and hnRNP LL which are required for repressing exon inclusion. We demonstrate that for both proteins, regions outside the RRMs, the N-terminal region, and a linker sequence between RRMs 2 and 3, are necessary for exon repression, but are only sufficient for repression in the case of hnRNP LL. In addition, both proteins require at least one RRM for maximal repression. Notably, we demonstrate that the region encompassing RRMs 1 and 2 of hnRNP LL imparts a second silencing activity not observed for hnRNP L. This additional functional component of hnRNP LL is consistent with the fact that the full-length hnRNP LL has a greater silencing activity than hnRNP L. Thus the results of the present study provide important insight into the functional and mechanistic variations that can exist between two highly related hnRNP proteins.

scholarly journals Cancer-Associated Substitutions in RNA Recognition Motifs of PUF60 and U2AF65 Reveal Residues Required for Correct Folding and 3′ Splice-Site Selection

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1865
Author(s):  
Jana Kralovicova ◽  
Ivana Borovska ◽  
Monika Kubickova ◽  
Peter J. Lukavsky ◽  
Igor Vorechovsky
Keyword(s):  
Rna Binding ◽  
Rna Recognition ◽  
Branch Points ◽  
Rna Recognition Motifs ◽  
Small Nuclear Ribonucleoprotein ◽  
Isoform Diversity ◽  
Protein Properties ◽  
Recognition Motifs ◽  
Nuclear Ribonucleoprotein ◽  
Mrna Isoform

U2AF65 (U2AF2) and PUF60 (PUF60) are splicing factors important for recruitment of the U2 small nuclear ribonucleoprotein to lariat branch points and selection of 3′ splice sites (3′ss). Both proteins preferentially bind uridine-rich sequences upstream of 3′ss via their RNA recognition motifs (RRMs). Here, we examined 36 RRM substitutions reported in cancer patients to identify variants that alter 3′ss selection, RNA binding and protein properties. Employing PUF60- and U2AF65-dependent 3′ss previously identified by RNA-seq of depleted cells, we found that 43% (10/23) and 15% (2/13) of independent RRM mutations in U2AF65 and PUF60, respectively, conferred splicing defects. At least three RRM mutations increased skipping of internal U2AF2 (~9%, 2/23) or PUF60 (~8%, 1/13) exons, indicating that cancer-associated RRM mutations can have both cis- and trans-acting effects on splicing. We also report residues required for correct folding/stability of each protein and map functional RRM substitutions on to existing high-resolution structures of U2AF65 and PUF60. These results identify new RRM residues critical for 3′ss selection and provide relatively simple tools to detect clonal RRM mutations that enhance the mRNA isoform diversity.

scholarly journals CoAA, a Nuclear Receptor Coactivator Protein at the Interface of Transcriptional Coactivation and RNA Splicing

2004 ◽  
Vol 24 (1) ◽  
pp. 442-453 ◽  
Author(s):  
Didier Auboeuf ◽  
Dennis H. Dowhan ◽  
Xiaotao Li ◽  
Kimberly Larkin ◽  
Lan Ko ◽  
...  
Keyword(s):  
Rna Splicing ◽  
Transcriptional Control ◽  
Transcriptional Activity ◽  
Molecular Mechanisms ◽  
Dependent Manner ◽  
Nuclear Receptor Coactivator ◽  
Rna Recognition Motifs ◽  
Transcriptional Coregulators ◽  
Recognition Motifs ◽  
Nuclear Ribonucleoprotein

ABSTRACT We have shown that steroid hormones coordinately control gene transcriptional activity and splicing decisions in a promoter-dependent manner. Our hypothesis is that a subset of hormonally recruited coregulators involved in regulation of promoter transcriptional activity also directly participate in alternative RNA splicing decisions. To gain insight into the molecular mechanisms by which transcriptional coregulators could control splicing decisions, we focused our attention on a recently identified coactivator, CoAA. This heterogeneous nuclear ribonucleoprotein (hnRNP)-like protein interacts with the transcriptional coregulator TRBP, a protein recruited to target promoters through interactions with activated nuclear receptors. Using transcriptional and splicing reporter genes driven by different promoters, we observed that CoAA mediates transcriptional and splicing effects in a promoter-preferential manner. We compared the activity of CoAA to the activity of other hnRNP-related proteins that, like CoAA, contain two N-terminal RNA recognition motifs (RRMs) followed by a C-terminal auxiliary domain and either have or have not been implicated in transcriptional control. By swapping either CoAA RRMs or the CoAA auxiliary domain with the corresponding domains of the proteins selected, we showed that depending on the promoter, the RRMs and the auxiliary domain of CoAA are differentially engaged in transcription. This contributes to the promoter-preferential effects mediated by CoAA on RNA splicing during the course of steroid hormone action.

scholarly journals Structure of the two most C-terminal RNA recognition motifs of PTB using segmental isotope labeling

2005 ◽  
Vol 25 (1) ◽  
pp. 150-162 ◽  
Author(s):  
Francesca Vitali ◽  
Anke Henning ◽  
Florian C Oberstrass ◽  
Yann Hargous ◽  
Sigrid D Auweter ◽  
...  
Keyword(s):  
Isotope Labeling ◽  
Rna Recognition ◽  
Rna Recognition Motifs ◽  
Segmental Isotope Labeling ◽  
Recognition Motifs
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