title: RNA-binding protein hnRNPLL regulates mRNA splicing and stability during B-cell to plasma-cell differentiation.
abstract: Posttranscriptional regulation is a major mechanism to rewire transcriptomes during differentiation. Heterogeneous nuclear RNA-binding protein LL (hnRNPLL) is specifically induced in terminally differentiated lymphocytes, including effector T cells and plasma cells. To study the molecular functions of hnRNPLL at a genome-wide level, we identified hnRNPLL RNA targets and binding sites in plasma cells through integrated Photoactivatable-Ribonucleoside-Enhanced Cross-Linking and Immunoprecipitation (PAR-CLIP) and RNA sequencing. hnRNPLL preferentially recognizes CA dinucleotide-containing sequences in introns and 3' untranslated regions (UTRs), promotes exon inclusion or exclusion in a context-dependent manner, and stabilizes mRNA when associated with 3' UTRs. During differentiation of primary B cells to plasma cells, hnRNPLL mediates a genome-wide switch of RNA processing, resulting in loss of B-cell lymphoma 6 (Bcl6) expression and increased Ig production--both hallmarks of plasma-cell maturation. Our data identify previously unknown functions of hnRNPLL in B-cell to plasma-cell differentiation and demonstrate that the RNA-binding protein hnRNPLL has a critical role in tuning transcriptomes of terminally differentiating B lymphocytes.
authors.affiliation: Divisions of Signaling and Gene Expression and Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037; and.
authors.forename: Xing
authors.initials: X
authors.lastname: Chang
authors.affiliation: Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Divisions of Signaling and Gene Expression and Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037; and Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093 arao@liai.org.
authors.forename: Anjana
authors.initials: A
authors.lastname: Rao
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics* / Q000378:metabolism; D007438:Introns / Q000235:genetics; D008810:Mice, Inbred C57BL; D059372:Nucleotide Motifs / Q000235:genetics; D010950:Plasma Cells / Q000378:metabolism*; D010954:Plasmacytoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D012313:RNA / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome
chemical_list: D020413:3' Untranslated Regions; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D012322:RNA Precursors; D012333:RNA, Messenger; C534662:hnRNPLL protein, mouse; D012313:RNA
keywords: PAR-CLIP; RNA binding proteins; alternative splicing; hnRNP; plasma cells
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