Identification of an AUUUA-specific messenger RNA binding protein.

An important control point in gene expression is at the level of messenger RNA (mRNA) stability. The mRNAs of certain regulatory cellular proteins such as oncogenes, cytokines, lymphokines, and transcriptional activators are extremely labile. These messages share a common AUUUA pentamer in their 3' untranslated region, which confers cytoplasmic instability. A cytosolic protein was identified that binds specifically to RNA molecules containing four reiterations of the AUUUA structural element. This protein consists of three subunits and binds rapidly to AUUUA-containing RNA. Such protein-RNA complexes are resistant to the actions of denaturing and reducing agents, demonstrating very stable binding. The time course, stability, and specificity of the protein-AUUUA interaction suggests the possibility that the formation of this complex may target susceptible mRNA for rapid cytoplasmic degradation.

[1]  R D Klausner,et al.  Oxidation-reduction and the molecular mechanism of a regulatory RNA-protein interaction. , 1989, Science.

[2]  C. Thompson,et al.  Regulation of lymphokine messenger RNA stability by a surface-mediated T cell activation pathway. , 1989, Science.

[3]  G. Brawerman.  mRNA decay: Finding the right targets , 1989, Cell.

[4]  G. Schuler,et al.  GM-CSF and oncogene mRNA stabilities are independently regulated in trans in a mouse monocytic tumor , 1988, Cell.

[5]  Richard Treisman,et al.  Removal of poly(A) and consequent degradation of c-fos mRNA facilitated by 3′ AU-rich sequences , 1988, Nature.

[6]  M. Yaniv,et al.  Transcriptional activation of c-jun during the G0/G1 transition in mouse fibroblasts , 1988, Nature.

[7]  G. Dreyfuss,et al.  Classification and purification of proteins of heterogeneous nuclear ribonucleoprotein particles by RNA-binding specificities , 1988, Molecular and cellular biology.

[8]  J. Ross,et al.  Poly(A) shortening and degradation of the 3' A+U-rich sequences of human c-myc mRNA in a cell-free system , 1988, Molecular and cellular biology.

[9]  T. Shenk,et al.  A 64 kd nuclear protein binds to RNA segments that include the AAUAAA polyadenylation motif , 1988, Cell.

[10]  G. Sonenshein,et al.  Transcriptional and posttranscriptional control of c-myc gene expression in WEHI 231 cells , 1986, Molecular and cellular biology.

[11]  G. Shaw,et al.  A conserved AU sequence from the 3′ untranslated region of GM-CSF mRNA mediates selective mRNA degradation , 1986, Cell.

[12]  M. Greenberg,et al.  Effect of protein synthesis inhibitors on growth factor activation of c-fos, c-myc, and actin gene transcription , 1986, Molecular and cellular biology.

[13]  N. Raj,et al.  Two levels of regulation of beta-interferon gene expression in human cells. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[14]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.