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5-PRIME,3-PRIME-EXORIBONUCLEASE 1; XRN1

5-PRIME,3-PRIME-EXORIBONUCLEASE 1; XRN1

Alternative titles; symbolsSTRAND EXCHANGE PROTEIN 1; SEP1HGNC Approved Gene Symbol: XRN1Cytogenetic location: 3q23 Genomic coordinates (GRCh38): 3:142,306,6...

Alternative titles; symbols

  • STRAND EXCHANGE PROTEIN 1; SEP1

HGNC Approved Gene Symbol: XRN1

Cytogenetic location: 3q23 Genomic coordinates (GRCh38): 3:142,306,609-142,448,061 (from NCBI)

▼ Cloning and Expression
By PCR using primers based on conserved yeast Sep1 sequences, followed by library screening and 3-prime RACE, Sato et al. (1998) cloned SEP1 from a peripheral blood leukocyte cDNA library. The deduced 1,694-amino acid protein has a calculated molecular mass of 190 kD. It shares 92% homology with mouse Sep1, which the authors called Dhm1, over the N-terminal and central portions of the molecule, but only 74% homology at the C terminus. Northern blot analysis detected a predominant 10-kb transcript in all cells and organs tested except lung, liver, and kidney. Minor bands of about 5.5 kb were detected in testis and placenta. Epitope-tagged SEP1 was recovered in the cytoplasmic fraction of transfected 293 cells and showed an apparent molecular mass of about 208 kD. Fluorescence-tagged SEP1 localized to the cytoplasm, particularly the nuclear periphery, of transfected HeLa cells.

Bashkirov et al. (1997) cloned 2 variants of mouse Sep1, which they called Xrn1. The longer protein contains 1,719 amino acids and has a calculated molecular mass of about 194 kD. The smaller variant contains a 13-amino acid deletion due to skipping of an optional exon.

▼ Gene Function
Bashkirov et al. (1997) characterized mouse Sep1. Both Sep1 variants were active in yeast complementation assays. The longer variant exhibited 5-prime-to-3-prime exoribonuclease activity. Sep1 showed substrate preference for RNA G4 tetraplex-containing substrates over a monomeric RNA substrate with the same sequence. It also preferred RNA substrates over DNA substrates, either G4 or monomeric. Immunostaining revealed endogenous SEP1 expressed in several human and murine cells as diffuse cytoplasmic staining and an enrichment in cytoplasmic foci. Microtubule depolymerizing agents abolished the diffuse cytoplasmic localization but not the localization in foci. Ingelfinger et al. (2002) determined that, in addition to SEP1, these foci contain RNA-decapping enzyme (DCP1/2) and several LSM proteins (see 607281).

Zhang et al. (2002) determined that SEP1 was downregulated in 3 of 4 osteogenic sarcoma cell lines and in 8 of 9 osteogenic sarcoma biopsy specimens.

▼ Mapping
By radiation hybrid analysis, Sato et al. (1998) mapped the XRN1 gene to chromosome 3q25-q26.1.

▼ Animal Model
Gatfield and Izaurralde (2004) showed that, contrary to expectation, degradation of premature termination codon (PTC)-containing messages in Drosophila is initiated by endonucleolytic cleavage(s) in the vicinity of the nonsense codon. The resulting 5-prime fragment is rapidly degraded by exonucleolytic digestion by the exosome, whereas the 3-prime fragment is degraded by Xrn1. This decay route is shown for several PTC-containing reporters, as well as an endogenous mRNA that is naturally regulated by nonsense-mediated mRNA decay (NMD). Gatfield and Izaurralde (2004) concluded that despite conservation in the NMD machinery, PTC-containing transcripts are degraded in Drosophila by a mechanism that differs considerably from those described in yeast and mammals.

Tags: 3q23