RNA, binding

Many human diseases are caused when certain proteins are either over- or underexpressed. Eor example, breast cancer can be induced by overexpressing certain cellular oncogenes within mammary tissue. To study the disease, researchers produce a line of transgenic mice that synthesize an abnormal amount of the same protein. This leads to symptoms of the disease in mice that are similar to what is found in humans. A protein can be overexpressed by inserting a DNA constmct with a strong promotor. Conversely, underexpression of a protein can be achieved by inserting a DNA constmct that makes antisense RNA. This latter blocks protein synthesis because the antisense RNA binds and inactivates the sense mRNA that codes for the protein. Once a line of mice is developed, treatments are studied in mice before these therapies are appHed to humans. 

In most four-helix bundle structures, including those shown in Figure 3.7, the a helices are packed against each other according to the "ridges in grooves" model discussed later in this chapter. However, there are also examples where coiled-coil dimers packed by the "knobs in holes" model participate in four-helix bundle structures. A particularly simple illustrative example is the Rop protein, a small RNA-binding protein that is encoded by certain plasmids and is involved in plasmid replication. The monomeric sub unit of Rop is a polypeptide chain of 63 amino acids built up from two... 

The coiled-coil structure of the leucine zipper motif is not the only way that homodimers and heterodimers of transcription factors are formed. As we saw in Chapter 3 when discussing the RNA-binding protein ROP, the formation of a four-helix bundle structure is also a way to achieve dimerization, and the helix-loop-helix (HLH) family of transcription factors dimerize in this manner. In these proteins, the helix-loop-helix region is preceded by a sequence of basic amino acids that provide the DNA-binding site (Figure 10.23), and... 

As it is the case in polypeptide folding, nonspecific or promiscuous RNA-binding proteins can prevent RNA mis-folding and resolve mis-foldedRNAs, thereby ensuring that RNA is accessible for its biological function [ 1 ]. Certain DEAD-box proteins as well as some proteins that are involved in the assembly of ribonuleoparticles were shown to act as RNA chaperones. 

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Bennasser Y, Yeung ML, Jeang KT (2006) HIV-1 TAR RNA subverts RNA interference in transfected cells through sequestration of TAR RNA-binding protein, TRBP. J Biol Chem 281(38) 27674-27678... 

Runge S, Nielsen FC, Nielsen J, Lykke-Andersen J, Wewer UM, Christiansen J 2000 HI 9 RNA binds four molecules of insulin-like growth factor II mRNA-binding protein. J Biol Chem... 

Chu E, Voeller D, Koeller DM et al. Identification of an RNA binding site for human thymidylate synthase. Proc Natl Acad Sci USA 1993 90 517-521. 

Nakagawa J, Nakagawa J, Moroni C. A 20-amino-acid autonomous RNA-binding domain contained in an enoyl-CoA hy-dratase. Eur J Biochem 1997 244 890-899. 

Nakagawa J, Meyer-Monard S, Hof-steenge J, Jeno P, Moroni C. AUH, a gene encoding an AU-specific RNA binding protein with intrinsic enoyl-CoA hy-dratase activity. Proc Natl Acad Sci USA 1995 92 2051-2055. 

Brennan LE, Egger D, Bienz K, MoroniC. Characterisation and mitochondrial localisation of AUH, an AU-specific RNA-binding enoyl-CoA hydra-tase. Gene 1999 228 85-91. 

Naranda, T., MacMillan, S. E., and Hershey, J. W. B. (1994). Purified yeast translational initiation factor eIF-3 is an RNA-binding protein complex that contains the PRT1 protein. J. Biol. Chem. 269, 32286—32292. 

Hofmann, I., Casella, M., Schnolzer, M., Schlechter, T., Spring, H., and Franke, W. W. (2006). Identification of the junctional plaque protein plakophilin 3 in cytoplasmic particles containing RNA-binding proteins and the recruitment of plakophilins 1 and 3 to stress granules. Mol. Biol. Cell 17, 1388—1398. 

Iseni, F., Garcin, D., Nishio, M., Kedersha, N., Anderson, P., and Kolakofsky, D. (2002). Sendai vims trailer RNA binds TIAR, a cellular protein involved in vims-induced apoptosis. EMBOJ. 21, 5141-5150. 

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