scholarly journals The RNA-binding protein HuR is required for maintenance of the germinal centre response

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ines C. Osma-Garcia ◽  
Dunja Capitan-Sobrino ◽  
Mailys Mouysset ◽  
Sarah E. Bell ◽  
Manuel Lebeurrier ◽  
...  
Keyword(s):  
B Cells ◽  
Rna Binding ◽  
Somatic Hypermutation ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Gene Signature ◽  
Germinal Centre ◽  
High Affinity ◽  
Dna Deamination ◽  
Splicing Patterns

AbstractThe germinal centre (GC) is required for the generation of high affinity antibodies and immunological memory. Here we show that the RNA binding protein HuR has an essential function in GC B cells to sustain the GC response. In its absence, the GC reaction and production of high-affinity antibody is severely impaired. Mechanistically, HuR affects the transcriptome qualitatively and quantitatively. The expression and splicing patterns of hundreds of genes are altered in the absence of HuR. Among these genes, HuR is required for the expression of Myc and a Myc-dependent transcriptional program that controls GC B cell proliferation and Ig somatic hypermutation. Additionally, HuR regulates the splicing and abundance of mRNAs required for entry into and transition through the S phase of the cell cycle, and it modulates a gene signature associated with DNA deamination protecting GC B cells from DNA damage and cell death.

scholarly journals The human RNA-binding protein and E3 ligase MEX-3C binds the MEX-3–recognition element (MRE) motif with high affinity

2017 ◽  
Vol 292 (39) ◽  
pp. 16221-16234 ◽  
Author(s):  
Lingna Yang ◽  
Chongyuan Wang ◽  
Fudong Li ◽  
Jiahai Zhang ◽  
Anam Nayab ◽  
...  
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
E3 Ligase ◽  
Recognition Element ◽  
High Affinity

scholarly journals The neuronal RNA binding protein Nova-1 recognizes specific RNA targets in vitro and in vivo.

1997 ◽  
Vol 17 (6) ◽  
pp. 3194-3201 ◽  
Author(s):  
R J Buckanovich ◽  
R B Darnell
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Motor Dysfunction ◽  
High Affinity ◽  
Loop Region ◽  
Nuclear Rna ◽  
Rna Ligands

Nova-1, an autoantigen in paraneoplastic opsoclonus myoclonus ataxia (POMA), a disorder associated with breast cancer and motor dysfunction, is a neuron-specific nuclear RNA binding protein. We have identified in vivo Nova-1 RNA ligands by combining affinity-elution-based RNA selection with protein-RNA immunoprecipitation. Starting with a pool of approximately 10(15) random 52-mer RNAs, we identified long stem-loop RNA ligands that bind to Nova-1 with high affinity (Kd of approximately 2 nM). The loop region of these RNAs harbors a approximately 15-bp pyrimidine-rich element [UCAU(N)(0-2)]3 which is essential for Nova-1 binding. Mutagenesis studies defined the third KH domain of Nova-1 and the [UCAU(N)(0-2)]3 element as necessary for in vitro binding. Consensus [UCAU (N)(0-2)], elements were identified in two neuronal pre-mRNAs, one encoding the inhibitory glycine receptor alpha2 (GlyR alpha2) and a second encoding Nova-1 itself. Nova-1 protein binds these RNAs with high affinity and specificity in vitro, and this binding can be blocked by POMA antisera. Moreover, both Nova-1 and GlyR alpha2 pre-mRNAs specifically coimmunoprecipitated with Nova-1 protein from brain extracts. Thus, Nova-1 functions as a sequence-specific nuclear RNA binding protein in vivo; disruption of the specific interaction between Nova-1 and GlyR alpha2 pre-mRNA may underlie the motor dysfunction seen in POMA.

scholarly journals Efficient homing of antibody-secreting cells to the bone marrow requires RNA-binding protein ZFP36L1

2020 ◽  
Vol 218 (3) ◽  
Author(s):  
Alexander Saveliev ◽  
Sarah E. Bell ◽  
Martin Turner
Keyword(s):  
Bone Marrow ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Receptor Kinase ◽  
High Affinity ◽  
Guidance Receptors ◽  
G Protein Coupled ◽  
Late Stages ◽  
Antibody Secreting Cells

Cell migration relies on coordinated activity of chemotactic and guidance receptors. Here, we report a specific role for the RNA-binding protein ZFP36L1 in limiting the abundance of molecules involved in the homing of antibody-secreting cells (ASCs) to the bone marrow (BM). In the absence of ZFP36L1, ASCs build up in the spleen and the liver and show diminished accumulation in the BM. ZFP36L1 facilitates migration by directly regulating G protein–coupled receptor kinase 2 (GRK2) and the integrin chains α4 and β1 in splenic ASCs. Expression of CXCR4 and of the integrins α4 and β1 is differentially regulated on ASCs produced at the early and late stages of the immune response. Consequently, deletion of the Zfp36l1 gene has a stronger effect on BM accumulation of high-affinity ASCs formed late in the response. Thus, ZFP36L1 is an integral part of the regulatory network controlling gene expression during ASC homing.

scholarly journals Post-Transcriptional Regulation of BCL2 mRNA by the RNA-Binding Protein ZFP36L1 in Malignant B Cells

PLoS ONE ◽  
2014 ◽  
Vol 9 (7) ◽  
pp. e102625 ◽  
Author(s):  
Anna Zekavati ◽  
Asghar Nasir ◽  
Amor Alcaraz ◽  
Maceler Aldrovandi ◽  
Phil Marsh ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
B Cells ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Post Transcriptional Regulation

scholarly journals FRAXE-associated mental retardation protein (FMR2) is an RNA-binding protein with high affinity for G-quartet RNA forming structure

2009 ◽  
Vol 37 (4) ◽  
pp. 1269-1279 ◽  
Author(s):  
Mounia Bensaid ◽  
Mireille Melko ◽  
Elias G. Bechara ◽  
Laetitia Davidovic ◽  
Antonio Berretta ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
High Affinity ◽  
Mental Retardation Protein

scholarly journals An ancient germ cell-specific RNA-binding protein protects the germline from cryptic splice site poisoning

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Ingrid Ehrmann ◽  
James H Crichton ◽  
Matthew R Gazzara ◽  
Katherine James ◽  
Yilei Liu ◽  
...  
Keyword(s):  
Germ Cell ◽  
Splice Site ◽  
Cell Biology ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Aberrant Splice ◽  
Splice Site Selection ◽  
Ambient Concentrations ◽  
Splicing Patterns

Male germ cells of all placental mammals express an ancient nuclear RNA binding protein of unknown function called RBMXL2. Here we find that deletion of the retrogene encoding RBMXL2 blocks spermatogenesis. Transcriptome analyses of age-matched deletion mice show that RBMXL2 controls splicing patterns during meiosis. In particular, RBMXL2 represses the selection of aberrant splice sites and the insertion of cryptic and premature terminal exons. Our data suggest a Rbmxl2 retrogene has been conserved across mammals as part of a splicing control mechanism that is fundamentally important to germ cell biology. We propose that this mechanism is essential to meiosis because it buffers the high ambient concentrations of splicing activators, thereby preventing poisoning of key transcripts and disruption to gene expression by aberrant splice site selection.

scholarly journals The Tissue-Specific RNA Binding Protein T-STAR Controls Regional Splicing Patterns of Neurexin Pre-mRNAs in the Brain

PLoS Genetics ◽  
2013 ◽  
Vol 9 (4) ◽  
pp. e1003474 ◽  
Author(s):  
Ingrid Ehrmann ◽  
Caroline Dalgliesh ◽  
Yilei Liu ◽  
Marina Danilenko ◽  
Moira Crosier ◽  
...  
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Tissue Specific ◽  
Splicing Patterns ◽  
The Brain
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