Sequence-specific RNA-binding proteins

Fig. 1.54 Principle of negative control of translation initiation by protein binding to mRNA. Proteins can negatively effect translation by binding to the sequences in the 5 non-translated region of their own or other mRNAs. The participating proteins are sequence-specific RNA binding proteins and recognize RNA sequences in hairpin structures or other secondary structures of RNA. The protein binding interferes with the scanning of ribosomes and prevents the translation of mRNA.

As shown in the example of ferritin mRNA, the binding of the ribosome to the 5 end of the mRNA can be blocked by RNA-binding proteins at the same region. This case is an example of a negative regulation of translation by sequence-specific RNA-binding proteins. Such proteins are categorized as translation repressors (see Fig. 1.46). 

Translational control by 3 end binding is often used in developmental processes to inactivate a specific mRNA at certain developmental stages. Examples are the Pumilio protein (review Parisi and Lin, 2000) and the fragile X mental retardation protein (review Kaytor and Orr, 2001) which are sequence-specific RNA binding proteins that bind to short RNA motifs at the 3-end of specific mRNA thereby inhibiting mRNA translation. 

Roberts WK, Hovanessian A, Brown RE, Clemens MJ, Kerr IM (1976) Interferon-mediated protein kinase and low-molecular-weight inhibitor of protein synthesis. Nature 264 477 80 Roller RJ, Roizman B (1990) The herpes simplex virus Us 11 open reading frame encodes a sequence-specific RNA-binding protein. J Virol 64 3463-3470 Roller RJ, Roizman B (1992) The herpes simplex virus 1 RNA binding protein US 11 is a virion component and associates with ribosomal 60S subunits. J Virol 66 3624-3632... 

Transcription is mediated and regulated by protein-DNA interactions, especially those involving the protein components of RNA polymerase (Chapter 26). We first consider how the activity of RNA polymerase is regulated, and proceed to a general description of the proteins participating in this process. We then examine the molecular basis for the recognition of specific DNA sequences by DNA-binding proteins. 

Members from the KorB domain family are characterized by the DNA-binding helix-turn-helix motif (a-3 and a-4). Examples of this protein domain family include the well-studied DNA-binding KorB domain protein, the three-dimensional structure of which has been solved with its operator (PDB accession code lr71, DNA/RNA-binding 3-helical bundle fold Fig. 2a). Amino acid residues outside the HTH motif (Thr-211 and Arg-240) determine the sequence-specific DNA binding (35) (Fig. 2a). 

Reines, D. and Mote, J., Jr. (1993) Elongation factor SH-dependent transcription by RNA polymerase II through a sequence-specific DNA-bind-ing protein. Proc. Natl. Acad. Sci. USA, 90, 1917-1921. 

Alternative splicing can be regulated by RNA-bIndIng proteins that bind to specific sequences near regulated... 

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