Abstract
AbstractLong noncoding RNAs (lncRNAs) are potentially important regulators of cell differentiation and development, but little is known about their roles in B lymphocytes. Using RNA-seq and de novo transcript assembly, we identified 4516 lncRNAs expressed in 11 stages of B-cell development and activation. Most of these lncRNAs have not been previously detected, even in the closely related T-cell lineage. Comparison with lncRNAs previously described in human B cells identified 185 mouse lncRNAs that have human orthologs. Using chromatin immunoprecipitation-seq, we classified 20% of the lncRNAs as either enhancer-associated (eRNA) or promoter-associated RNAs. We identified 126 eRNAs whose expression closely correlated with the nearest coding gene, thereby indicating the likely location of numerous enhancers active in the B-cell lineage. Furthermore, using this catalog of newly discovered lncRNAs, we show that PAX5, a transcription factor required to specify the B-cell lineage, bound to and regulated the expression of 109 lncRNAs in pro-B and mature B cells and 184 lncRNAs in acute lymphoblastic leukemia.
Highlights
IntroductionLnc-DC is required for normal dendritic cell differentiation and function,[1] IL1b-enhancer-associated lncRNAs (eRNAs) and IL1b-RBT46 are required for lipopolysaccharide-induced pro-inflammatory responses in monocytes,[2] and NRAV modulates cellular responses to viral infections.[3] In T cells, an intronic Long noncoding RNAs (lncRNAs) NRON abrogates the nuclear transport of nuclear factor of activated T cells, and modulates expression of interleukin-2.4 In B-cell lymphomas, the lncRNA Fas-AS1 modulates expression of soluble Fas receptor messenger RNA, an important regulator of apoptosis.[5] lncRNAs have the potential to influence both normal and pathological immune cell development and function
Long noncoding RNAs have emerging roles in innate and adaptive immunity
To aid in the identification of Long noncoding RNAs (lncRNAs) active within the immune system, we present a comprehensive catalog of 4516 lncRNAs, including 2349 intergenic loci, expressed across 11 murine B-cell populations
Summary
Lnc-DC is required for normal dendritic cell differentiation and function,[1] IL1b-eRNA and IL1b-RBT46 are required for lipopolysaccharide-induced pro-inflammatory responses in monocytes,[2] and NRAV modulates cellular responses to viral infections.[3] In T cells, an intronic lncRNA NRON abrogates the nuclear transport of nuclear factor of activated T cells, and modulates expression of interleukin-2.4 In B-cell lymphomas, the lncRNA Fas-AS1 modulates expression of soluble Fas receptor messenger RNA, an important regulator of apoptosis.[5] lncRNAs have the potential to influence both normal and pathological immune cell development and function. Enhancer-associated lncRNAs (eRNAs) act in cis and originate from transcribed extragenic or intragenic enhancer regions, whereas promoter-associated lncRNAs (pRNAs) can act in trans and originate from canonical promoter-derived transcriptional activity.[7,8]
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