Proteomics

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A multiomics framework for high-throughput lncRNA characterization uncovers major immune regulators

ABSTRACT: Long noncoding RNAs (lncRNAs) play crucial roles in eukaryotic biology, yet their functions in the immune system are not fully understood. This study presents a comprehensive resource on the regulation, pathway dependencies, subcellular localizations, and protein interactomes of lncRNAs in immune cells exposed to pathogens. We developed GRADR, a methodology combining gradient profiling and RNA-bound proteome analysis, to map interactomes for all expressed RNAs in a single experiment. Using GRADR and targeted CRISPR multiomics, we identified a network of lncRNAs, including LINC01215, AC022816, and LINC01268 (ROCKI), that influence immunity, mainly through interactions with splicing factors. Our data are compiled into SMyLR, a web interface providing access to our lncRNA regulation and interactome atlas. This resource is expected to significantly advance research into RNA regulation in immunity.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Macrophage

DISEASE(S): Disease Free

SUBMITTER: Uwe Linne  

LAB HEAD: Uwe Linne

PROVIDER: PXD053952 | Pride | 2025-10-01

REPOSITORIES: Pride

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210503_DR_049_Sh_1a_Slot1-30_1_6690.d.zip Other
210503_DR_049_Sh_1b_Slot1-30_1_6702.d.zip Other
210503_DR_049_Sh_2a_Slot1-31_1_6695.d.zip Other
210503_DR_049_Sh_2b_Slot1-31_1_6707.d.zip Other
210503_DR_049_Sh_3a_Slot1-32_1_6691.d.zip Other
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Publications

Long noncoding RNAs (lncRNA) are crucial yet underexplored regulators of human immunity. Here we develop GRADR, a method integrating gradient profiling with RNA-binding proteome analysis, to map the protein interactomes of all expressed RNAs in a single experiment to study mechanisms of lncRNA-mediated regulation of human primary macrophages. Applying GRADR alongside CRISPR-multiomics, we reveal a network of NFκB-dependent lncRNAs, including LINC01215, AC022816.1 and ROCKI, which modulate distin  ...[more]

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