scholarly journals RRM domain of ALS/FTD-causing FUS interacts with membrane: an anchor of membraneless organelles to membranes?

2017 ◽  
Author(s):  
Yimei Lu ◽  
Liangzhong Lim ◽  
Jianxing Song
Keyword(s):  
Significant Interaction ◽  
Bilayer Membrane ◽  
Rna Recognition Motif ◽  
Rna Recognition ◽  
Large Network ◽  
Sequence Complexity ◽  
Recognition Motif ◽  
Rrm Domain ◽  
In Cells

Abstract526-residue FUS functions to self-assemble into reversible droplets/hydrogels, which could be further solidified into pathological fibrils. FUS is composed of N-terminal low-sequence complexity (LC); RNA-recognition motif (RRM) and C-terminal LC domains. FUS belongs to an emerging category of proteins which are capable of forming membraneless organelles in cells via phase separation. On the other hand, eukaryotic cells contain a large network of internal membrane systems. Therefore, it is of fundamental importance to address whether membraneless organelles can interact with membranes. Here we attempted to explore this by NMR HSQC titrations of three FUS domains with gradual addition of DMPC/DHPC bicelle, which mimics the bilayer membrane. We found that both N- and C-terminal LC domains showed no significant interaction with bicelle, but its well-folded RRM domain does dynamically interact with bicelle with an interface opposite to that for binding nucleic acids including RNA and ssDNA. If this in vitro observation also occurs in cells, to interact with membrane might represent a mechanism for dynamically organizing membraneless organelles to membranes to facilitate their physiological functions.

scholarly journals Engineered Exosomes for the Targeted Delivery of a Novel Therapeutic Cargo to Enhance Sorafenib-Mediated Ferroptosis in Hepatocellular Carcinoma.

2021 ◽  
Author(s):  
Xiaoju Li ◽  
Qianqian Yu ◽  
Xinyan Guo ◽  
Chenlin Liu ◽  
Runze Zhao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Targeted Delivery ◽  
Rna Recognition Motif ◽  
Advanced Hepatocellular Carcinoma ◽  
Rna Recognition ◽  
Sorafenib Treatment ◽  
Recognition Motif ◽  
Interfering Rna

Abstract Background Sorafenib is one of the few effective first-line drugs approved for the treatment of advanced hepatocellular carcinoma (HCC). However, the development of drug resistance is common among individuals with HCC. Thus, there is an urgent need to solve this problem. Results Recent evidence indicated that the anticancer activity of sorafenib mainly relies on the induction of ferroptosis. In our study, genes that suppress ferroptosis, especially GPX4 and DHODH, were enriched in sorafenib-resistant cells and primary tissues and were associated with poor prognosis of HCC patients who received sorafenib treatment. Therefore, silencing GPX4 and DHODH might be a novel and effective strategy to overcome sorafenib resistance. Here, a novel ferroptosis inducer comprising a multiplex small interfering RNA (multi-siRNA) capable of simultaneously silencing GPX4 and DHODH was created. Then, exosomes with high multi-siRNA loading and HCC-specific targeting were established by fusing the SP94 peptide and the N-terminal RNA recognition motif (RRM) of U1-A with the exosomal membrane protein Lamp2b. The results from the in vitro and in vivo experiments indicate that this tumor-targeting nanodelivery system (ExoSP94−lamp2b−RRM-multi-siRNA) could enhance sorafenib-induced ferroptosis and overcome sorafenib resistance, which might open a new avenue for clinically overcoming sorafenib resistance. Conclusions We designed HCC-targeted exosomes (ExoSP94−Lamp2b−RRM) that can deliver a novel ferroptosis inducer. Our data show that ExoSP94−lamp2b−RRM-multi-siRNA could enhance sorafenib-induced ferroptosis by silencing GPX4 and DHODH expression and consequently increase HCC sensitivity to sorafenib. This is the first study to describe the use of engineered exosomes to overcome acquired sorafenib resistance with respect to ferroptosis.

Rice MEL2, the RNA recognition motif (RRM) protein, binds in vitro to meiosis-expressed genes containing U-rich RNA consensus sequences in the 3′-UTR

2015 ◽  
Vol 89 (3) ◽  
pp. 293-307 ◽  
Author(s):  
Saori Miyazaki ◽  
Yutaka Sato ◽  
Tomoya Asano ◽  
Yoshiaki Nagamura ◽  
Ken-Ichi Nonomura
Keyword(s):  
Rna Recognition Motif ◽  
Rna Recognition ◽  
Consensus Sequences ◽  
Recognition Motif

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.

A conserved RNA recognition motif (RRM) domain of Brassica napus FCA improves cotton fiber quality and yield by regulating cell size

2011 ◽  
Vol 30 (1) ◽  
pp. 93-101 ◽  
Author(s):  
Fan Sun ◽  
Chuanliang Liu ◽  
Chaojun Zhang ◽  
Weiwei Qi ◽  
Xueyan Zhang ◽  
...  
Keyword(s):  
Brassica Napus ◽  
Cell Size ◽  
Cotton Fiber ◽  
Fiber Quality ◽  
Rna Recognition Motif ◽  
Rna Recognition ◽  
Recognition Motif ◽  
Rrm Domain ◽  
Cotton Fiber Quality

scholarly journals RNA Recognition Motif 2 of Yeast Pab1p Is Required for Its Functional Interaction with Eukaryotic Translation Initiation Factor 4G

1998 ◽  
Vol 18 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Steven H. Kessler ◽  
Alan B. Sachs
Keyword(s):  
Translation Initiation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Rna Recognition Motif ◽  
Rna Recognition ◽  
Eukaryotic Translation ◽  
Recognition Motif ◽  
Amino Acid Region ◽  
Eukaryotic Translation Initiation

ABSTRACT The eukaryotic mRNA 3′ poly(A) tail and its associated poly(A)-binding protein (Pab1p) are important regulators of gene expression. One role for this complex in the yeast Saccharomyces cerevisiae is in translation initiation through an interaction with a 115-amino-acid region of the translation initiation factor eIF4G. The eIF4G-interacting domain of Pab1p was mapped to its second RNA recognition motif (RRM2) in an in vitro binding assay. Moreover, RRM2 of Pab1p was required for poly(A) tail-dependent translation in yeast extracts. An analysis of a site-directed Pab1p mutation which bound to eIF4G but did not stimulate translation of uncapped, polyadenylated mRNA suggested additional Pab1p-dependent events during translation initiation. These results support the model that the association of RRM2 of yeast Pab1p with eIF4G is a prerequisite for the poly(A) tail to stimulate the translation of mRNA in vitro.

Solution Structure of the Second RNA Recognition Motif (RRM) Domain of Murine T Cell Intracellular Antigen-1 (TIA-1) and Its RNA Recognition Mode†‡

Biochemistry ◽  
2008 ◽  
Vol 47 (24) ◽  
pp. 6437-6450 ◽  
Author(s):  
Kanako Kuwasako ◽  
Mari Takahashi ◽  
Naoya Tochio ◽  
Chikage Abe ◽  
Kengo Tsuda ◽  
...  
Keyword(s):  
T Cell ◽  
Solution Structure ◽  
Rna Recognition Motif ◽  
Rna Recognition ◽  
Recognition Motif ◽  
Rrm Domain ◽  
Intracellular Antigen

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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