Sequence-specific RNA-binding

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... 

The amino acid 58 was used in the solid-phase synthesis of sequence-specific DNA binding polyamides containing N-methylimidazole and N-methylpyrrole amino acids <96JACS6141> and it was also reported that the imidazole-acridine conjugate 59 could effectively catalyze the cleavage of t-RNA <96TL4417>. 

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. 

Many short-lived mRNAs in mammalian cells contain multiple, sometimes overlapping, copies of the sequence AUUUA in their 3 untranslated region. Specific RNA-bIndIng... 

Lagrange, T., Kapanidis, A. N., Tang, H., Reinberg, D., and Ebright, R. H. (1998). New core promoter element in RNA polymerase II dependent transcription sequence specific DNA binding by transcription factor IIB. Genes Dev. 12(1), 34-44. 

EcoRV is a hydrolase enzyme that belongs to the nuclease enzymes (EC 3.1) and is responsible for cleaving the P-O bond of phosphodiester in DNA and RNA. Exonuclease enzymes hydrolyze the P-O phosphodiester bond of the terminal mononucleotide and are not sequence specific [31]. Endonuclease enzymes include both examples, that is, enzymes that are not sequence specific and those that are sequence specific (e.g., type II restriction endonucleases) [32]. Type II restriction endonucleases in bacteria, archaea, and algae use their sequence specificity to bind and cleave the foreign DNA of invading viruses. These enzymes are especially interesting, as they combine their remarkable sequence specificity with high catalytic rates of phosphodiester hydrolysis. 

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