Widespread intronic polyadenylation diversifies immune cell transcriptomes.
Nat Commun
; 9(1): 1716, 2018 04 30.
Article
in En
| MEDLINE
| ID: mdl-29712909
ABSTRACT
Alternative cleavage and polyadenylation (ApA) is known to alter untranslated region (3'UTR) length but can also recognize intronic polyadenylation (IpA) signals to generate transcripts that lose part or all of the coding region. We analyzed 46 3'-seq and RNA-seq profiles from normal human tissues, primary immune cells, and multiple myeloma (MM) samples and created an atlas of 4927 high-confidence IpA events represented in these cell types. IpA isoforms are widely expressed in immune cells, differentially used during B-cell development or in different cellular environments, and can generate truncated proteins lacking C-terminal functional domains. This can mimic ectodomain shedding through loss of transmembrane domains or alter the binding specificity of proteins with DNA-binding or protein-protein interaction domains. MM cells display a striking loss of IpA isoforms expressed in plasma cells, associated with shorter progression-free survival and impacting key genes in MM biology and response to lenalidomide.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Plasma Cells
/
Introns
/
Immunoglobulin mu-Chains
/
Polyadenylation
/
Transcriptome
/
Heavy Chain Disease
/
Multiple Myeloma
Type of study:
Observational_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2018
Document type:
Article
Affiliation country:
United States