Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
To better understand intranuclear-targeting mechanisms, we have studied the transport of U3 snoRNA in human cells. Surprisingly, we found that PHAX, the snRNA export adaptor, is highly enriched in complexes containing m7G-capped U3 precursors. In contrast, the export receptor CRM1 is predominantly bound to TMG-capped U3 species. In agreement, PHAX does not export m7G-capped U3 precursors because their caps become hypermethylated in the nucleus. Inactivation of PHAX and CRM1 shows that U3 first requires PHAX to reach Cajal bodies, and then CRM1 to be routed from there to nucleoli. Furthermore, PHAX also binds the precursors of U8 and U13 box C/D snoRNAs and telomerase RNA. PHAX was previously shown to discriminate between small versus large RNAs during export. Our data indicate that the role of PHAX in determining the identity of small RNAs extends to nonexported species, and this appears critical to promote their transport within the nucleus.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.molcel.2004.11.013 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Structural basis for the synergistic assembly of the snRNA export complex.
Nat Struct Mol Biol
August 2025
European Molecular Biology Laboratory, Grenoble, France.
The nuclear cap-binding complex (CBC) and its partner Arsenite-Resistance Protein 2 (ARS2) regulate the fate of RNA polymerase II transcripts via mutually exclusive interactions with RNA effectors. One such effector is PHAX, which mediates the nuclear export of U-rich small nuclear RNAs (snRNAs). Here we present the cryo-electron microscopy structure of the human snRNA export complex comprising phosphorylated PHAX, CBC, CRM1-RanGTP and capped RNA.
View Article and Find Full Text PDFPHAX enhanced LIN28B-mediated PBX3 mRNA stability to promote esophageal cancer development.
Cancer Sci
March 2025
Department of Gastroenterology, Second Xiangya Hospital, Central South University, Changsha, China.
The abnormal expression of PHAX was observed in esophageal cancer, however, its specific function and mechanism remain to be further elucidated. We demonstrated that PHAX, LIN28B, and PBX3 were upregulated in esophageal cancer, while TET2 was downregulated. Elevated PHAX correlated with adverse outcomes among esophageal cancer patients.
View Article and Find Full Text PDFRNA 3'end tailing safeguards cells against products of pervasive transcription termination.
Nat Commun
December 2024
Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
Article Synopsis
- - Premature transcription termination leads to the accumulation of unadenylated RNA, which the NEXT complex typically degrades, but alternative degradation pathways are not well understood.
- - Upon inactivation of NEXT, there is an increase in 3' end uridylated and adenylated RNAs, with short U-tailed RNAs modified by TUT4/7 and longer RNAs adenylated by enzymes like TENT2.
- - These RNAs are degraded through different mechanisms, including the PAXT pathway in the nucleus or the cytoplasmic exosome, where failure to degrade them can result in reduced translation and cell death.
Nuclear sorting of short RNA polymerase II transcripts.
Mol Cell
October 2024
Department of Molecular Biology and Genetics, Aarhus University, Universitetsbyen 81, Aarhus, Denmark. Electronic address:
Mammalian genomes produce an abundance of short RNA. This is, to a large extent, due to the genome-wide and spurious activity of RNA polymerase II (RNAPII). However, it is also because the vast majority of initiating RNAPII, regardless of the transcribed DNA unit, terminates within a ∼3-kb early "pausing zone.
View Article and Find Full Text PDFThe RNA helicase DDX39 contributes to the nuclear export of spliceosomal U snRNA by loading of PHAX onto RNA.
Nucleic Acids Res
September 2024
Institute for Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
RNA helicases are involved in RNA metabolism in an ATP-dependent manner. Although many RNA helicases unwind the RNA structure and/or remove proteins from the RNA, some can load their interacting proteins onto RNAs. Here, we developed an in vitro strategy to identify the ATP-dependent factors involved in spliceosomal uridine-rich small nuclear RNA (U snRNA) export.
View Article and Find Full Text PDF