Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

AUF1 (A+U-rich RNA binding factor) participates in the rapid decay of mRNAs in the cytoplasm. It is sometimes called heterogeneous nuclear ribonucleoprotein (hnRNP) D0; however, evidence for its characterization as an hnRNP protein has been scarce. S1 proteins A-D are those selectively extracted at pH 4.9 from isolated nuclei pretreated with either RNase A or DNase I. In the present study we identified S1 ('first supernatant') proteins B2, C1 and D1 with p45, p40 and p37 AUF1s respectively, by microsequencing and product analysis of transfected cDNAs. We found, further, that more than 96% of the S1 proteins occurred in the nucleus, and localized largely in RNase-sensitive structures. B2 was confined in the nucleus and C1 directly bound to heterogeneous nuclear RNAs (hnRNAs). These B2 and C1 proteins formed hnRNP structures responsible for the 33 S, and, to lesser extent, the 40 S particles, which were liberated upon mild nucleolytic cleavage. On the other hand, D1 and the remainder of C1 were associated with nuclease-hypersensitive sites of hnRNAs, and comprised the major cytoplasmic AUF1s that may be involved in mRNA decay. Two-dimensional immunoblotting resolved each S1 isoform into up to six spots or more, and suggested that the previous uncertain relationship of hnRNP D0 and hnRNP D is resolved in terms of charge differences and differential splicing arising from one gene. The present results thus indicate that S1 proteins B2, C1 and D1 are identical with AUF1 proteins, but largely occur as hnRNP proteins in the nucleus. That hnRNP D0 is indeed an hnRNP protein was verified.
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PMID:Identification of S1 proteins B2, C1 and D1 as AUF1 isoforms and their major role as heterogeneous nuclear ribonucleoprotein proteins. 1262 34

An AU-rich element (ARE) located in the 3'-untranslated region of many short-lived mRNAs functions as an instability determinant for these transcripts. AUF1/hnRNP D, an ARE-binding protein family consisting of four isoforms, promotes rapid decay of ARE-mRNAs. The mechanism by which AUF1 promotes rapid decay of ARE-mRNA is unclear. AUF1 has been shown to form an RNase-resistant complex in cells with the cap-initiation complex and heat shock proteins Hsp70 and Hsc70, as well as other unidentified factors. To understand the function of the AUF1 complex, we have biochemically investigated the association of AUF1 with the components of the translation initiation complex. We used purified recombinant proteins and a synthetic ARE RNA oligonucleotide to determine the hierarchy of protein interactions in vitro and the effect of AUF1 binding to the ARE on the formation of protein complexes. We demonstrate that all four AUF1 protein isoforms bind directly and strongly to initiation factor eIF4G at a C-terminal site regardless of AUF1 interaction with the ARE. AUF1 is shown to directly interact with poly(A) binding protein (PABP), both independently of eIF4G and in a complex with eIF4G. AUF1-PABP interaction is opposed by AUF1 binding to the ARE or Hsp70 heat shock protein. In vivo, AUF1 interaction with PABP does not alter PABP stability. Based on these and other data, we propose a model for the molecular interactions of AUF1 that involves translation-dependent displacement of AUF1-PABP complexes from ARE-mRNAs with possible unmasking of the poly(A) tail.
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PMID:Assembly of AUF1 with eIF4G-poly(A) binding protein complex suggests a translation function in AU-rich mRNA decay. 1655 36