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Series GSE267857 Query DataSets for GSE267857
Status Public on Jul 29, 2024
Title A nuclear RNA degradation code for eukaryotic transcriptome surveillance
Organism Homo sapiens
Experiment type Other
Summary The RNA exosome is an RNA degradation machine that is critical for eukaryotic transcriptome surveillance and mutations in exosome components cause numerous human diseases. The exosome is directed to specific RNAs by adaptor protein complexes. However, it remains unclear how these adaptors specifically recognize their target RNAs. The PAXT connection is an adaptor that recruits the exosome to polyadenylated RNAs in the nucleus, especially transcripts polyadenylated at intronic poly(A) sites. Here we show that PAXT-mediated degradation is induced by the combination of a 5′ splice site and a poly(A) junction, which includes the poly(A) signal and the poly(A) tail, but not by either sequence alone. These two sequences are bound by the splicing factor U1 snRNP and pre-mRNA 3′ processing factors, which in turn cooperatively recruit PAXT. As 5′ splice sites and poly(A) junctions are typically found on unspliced precursors and processed RNAs respectively, we propose that their presence on the same RNA molecule constitutes an “RNA degradation code”. Consistent with this model, disease-associated single nucleotide polymorphisms that create novel 5′ splice sites near poly(A) sites induce aberrant RNA degradation. Our results revealed the first nuclear RNA degradation code that plays important roles in transcriptome surveillance and may also influence gene evolution.
 
Overall design Examination of 16 samples by PAS-seq, a type of 3′ end mRNA-sequencing. There are 3 biological replicates of control siRNA treatment, 3 biological replicates of EXOSC3 siRNA treatment, 3 biological replicates of scramble shRNA treatment, 2 biological replicates of MTR4 shRNA treatment, 3 biological replicates of ZFC3H1 shRNA treatment, and 2 biological replicates of PABPN1 shRNA treatment. All samples were prepared from HEK293T cells.
 
Contributor(s) Soles LV, Shi Y
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Submission date May 20, 2024
Last update date Jul 30, 2024
Contact name Yongsheng Shi
E-mail(s) yongshes@uci.edu
Phone 9498248847
Organization name UC Irvine
Department Microbiology & Molecular Genetics
Lab Shi
Street address 811 Health Sciences Road, Medical Sciences B Room 262
City Irvine
State/province California
ZIP/Postal code 92697
Country USA
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (16)
GSM8279914 HEK293T Control siRNA PAS-seq Replicate 1
GSM8279915 HEK293T Control siRNA PAS-seq Replicate 2
GSM8279916 HEK293T Control siRNA PAS-seq Replicate 3
Relations
BioProject PRJNA1113537

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Supplementary file Size Download File type/resource
GSE267857_RAW.tar 277.6 Mb (http)(custom) TAR (of BW)
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Raw data are available in SRA

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