Ribonucleoprotein

Despite the unity in secondary structural patterns, little is known about the three-dimensional, or tertiary, structure of rRNAs. Even less is known about the quaternary interactions that occur when ribosomal proteins combine with rRNAs and when the ensuing ribonucleoprotein complexes, the small and large subunits, come together to form the complete ribosome. Furthermore, assignments of functional roles to rRNA molecules are still tentative and approximate. (We return to these topics in Chapter 33.)... 

Telomerase Ribonucleoprotein Suppression of telomerase activity inhibition of cell proliferation change in morphology induction of apoptosis... 

Ribosomes are ancient ribonucleoprotein complexes that are the sites of protein synthesis in living cells. Their core structures and fundamental functional mechanisms have been conserved throughout the three domains of life bacteria, archaea and eukaryotes. All ribosomes are organized into two subunits that are defined by their apparent sedimentation coefficient, measured in Svedberg units (S). There is a general... 

The signal recognition particle (SRP) is a cytosolic ribonucleoprotein complex which binds to signal sequences of nascent membrane and secretory proteins emerging from ribosomes. The SRP consists of a 7S RNA and at least six polypeptide subunits (relative molecular masses 9, 14, 19, 54, 68, and 72 kD). It induces an elongation arrest until the nascent chain/ ribosome/SRP complex reaches the translocon at the endoplasmic reticulum (ER) membrane. 

HS also affects ribonucleoproteins. Overall, there is a decrease in the pro-tein/RNA ratio. Antibodies against certain ribonucleoproteins have been used as a probe in heat shocked cells and these demonstrate a loss of some RNA particles normally seen at 37 °C. 

Recently, the related phenomenon of RNA interference (RNAi) has attracted much attention [5]. RNAi occurs when a short (generally 21 nucleotides in length) double-stranded RNA (dsRNA) catalyticaUy represses the translation of a fully complementary mRNA sequence. The process appears to proceed via a complex formed between the antisense RNA strand and a protein with RNase activity [6]. Upon binding to the target mRNA sequence, the ribonucleoprotein complex initiates cleavage of the mRNA transcript thus preventing translation of intact protein. After dissociation from the truncated mRNAs, the ribonucleoprotein complex is free to act on other intact mRNAs. Such small interfering RNAs (siRNAs) have... 

In terms of their molecular structures, the nucleotide and protein realms are usually considered to be rather independent of each other. However, these two families of molecules are covalently linked in the translational aminoacyl- RNAs and ribonucleoproteins as well as in the nucleoproteins involved in cellular and viral replication. In these hybrid biomolecules, a (deoxy)ribose phosphate moiety serves as the structural connection between the nucleoside and peptide moieties. 

A large number of discrete, highly conserved, and small stable RNA species are found in eukaryotic cells. The majority of these molecules are complexed with proteins to form ribonucleoproteins and are distributed in the nucleus, in the cytoplasm, or in both. They range in... 

In the past, dissociation of the nucleoprotein complex has been brought about by salt solutions or by heat denaturation,129 but, more recently, decomposition has been effected by hydrolysis with trypsin,126 or by the use of dodecyl sodium sulfate130 or strontium nitrate.131 Some virus nucleoproteins are decomposed by ethyl alcohol.132 This effect may be similar to that of alcohol on the ribonucleoproteins of mammalian tissues. If minced liver is denatured with alcohol, and the dried tissue powder is extracted with 10% sodium chloride, the ribonucleoproteins are decomposed to give a soluble sodium ribonucleate while the deoxyribonucleoproteins are unaffected.133 On the other hand, extraction with 10 % sodium chloride is not satisfactory unless the proteins have first been denatured with alcohol. Denaturation also serves to inactivate enzymes of the tissues which might otherwise bring about degradation of the nucleic acid during extraction. 

Once the amino acid has been bound to its tRNA, it can pass to the next phase of protein synthesis, involving its interaction with mRNA, which takes place on the ribosome, a molecular machine of enormous complexity. The ribosome of E. coli is a ribonucleoprotein assembly of molecular weight 2700 kDa, and sedimentation constant of 70S9. It is made up of roughly two-thirds RNA and one-third protein, and can be separated into a small (30S) and a large (50S) subunit. The 30S subunit contains 21 proteins and one 16S RNA molecule, while the large subunit has 34 different proteins and two RNA molecules, one 23S and one 5S. Despite its size and complexity, the structure of both ribosomal subunits has been determined to atomic resolution (Figure 4.32), and very recently the atomic structure of the 70S ribosome has been determined at 2.8 A resolution (Selmer et al., 2006). 

The Xenopus transcription factor IIIA not only acts as an essential RNA polymerase transcription factor for the expression of the 5S rRNA gene, it also binds to the 5S rRNA to form a 7S ribonucleoprotein particle that stabilizes the RNA until it is required for ribosome assembly and facilitates nuclear export of the 5S rRNA. Indeed, it was originally shown to be the protein component associated with 5S rRNA in the 7S particle in Xenopus oocytes before it was recognized as a transcription factor. How, we may ask, can this protein not only recognize specific DNA sequences in the 5S rRNA gene upstream region, but also recognize different, but equally specific, sequences in 5S rRNA ... 

Ferro A, Olivera B (1982) Poly(ADP-ribosylation) in vitro. J Biol Chem 257 7808-7813 Gagne JP, Hunter JM, Labrecque B, Chabot B, Poirier GG (2003) A proteomic approach to the identification of heterogeneous nuclear ribonucleoproteins as a new family of poly(ADP-ribose)-binding proteins. Biochem J 371 331-340... 

The removal of introns from pre-messenger RNAs in eukaryotes is catalyzed by the spliceosome, which is a large ribonucleoprotein consisting of at least 70 proteins and five small nuclear RNAs (snRNA) [144]. This splicing pathway involves two phosphotransfer reactions. In the first step, the 5 splice site is attacked by a 2 hydroxy group of an adenosine nucleotide within the intron [indicated by A in Fig. 12] that corresponds to the branch point in the lariat intermediate (Fig. 12,middle). In the second step, the 3 -OH group of the free 5 exon attacks the phosphodiester bond between the intron and... 

The transcription of the DNA gives three kinds of RNA ribosomal, messenger, and transfer. The most abundant RNA is rRNA. Most rRNAs are large and are found in combination with proteins in the ribonucleoprotein complexes called ribosomes. Ribosomes are subcellular sites for protein synthesis. 

The dictyodendrin class of carbazole alkaloids (see Schemes 2.70 and 2.71) completely inhibit telomerase activity (at a concentration of 50 pg/mL). It is known that 90% of human tumors show telomerase activity, which is absent in normal cells. Telemorase is a ribonucleoprotein enzyme that adds repeating known telomers to the DNA sequence (251). 

B. Ribosomes are the ribonucleoprotein machines that translate the mRNA into... 

T2. Tewari, M., Beidler, D. R., and Dixit, V. M., CrmA-inhibitable cleavage of the 70-kDa protein component of the U1 small nuclear ribonucleoprotein during Fas- and tumor necrosis factor-induced apoptosis. J. Biol. Chem. 270, 18738-18741 (1995). 

Their mechanism of action involves inhibition of the viral M2 protein, an integral membrane protein that acts as a H channel Blockade of the M2 protein prevents the acid-mediated dissociation of the ribonucleoprotein complex that occurs early in replication. In certain strains, the pH changes that result from M2 inhibition alter the conformation of hemagglutinin, hence inhibit viral assembly. 

Neubauer, G., Gottschalk, A., Fabrizio, P., Seraphin, B., Luhrmann, R., and Mann, M. (1997) Identification of the proteins of the yeast U1 small nuclear ribonucleoprotein complex by mass spectrometry. Proc Natl Acad Sci USA 94 385-390. 

The final principal component of the cell is the nucleus. This is located in the center of the cell and is surrounded by a double membrane, the outer layer being derived from the ER of the cytoplasm and the inner layer coming from the nucleus itself. The two leaflets of the double membrane are fused in places, producing nuclear pores that enable the transfer of macromolecules from the cytoplasm to the nucleus. Two important components of the nucleus are chromatin and the nucleolus. Chromatin represents polymers of DNA complexed with protein. The nucleolus is a complex substructure, composed of ribonucleoprotein granules, that controls the synthesis of RNA destined to form the ribosomes of the cytoplasm. Cells engaged heavily in protein synthesis have... 

Splicing occurs in a large protein-nucleic acid complex, termed the spUceosome. Components of the spliceosome are, apart from the pre-mRNA, a number of proteins and small RNAs, termed the Ul, U2, U4, U5 and U6. The RNAs found in the spUceo-some are bound to specific proteins. The complexes are termed snRNPs (small nuclear ribonucleoprotein). Depending upon the type of RNA bound, there are Ul, U2, U5 and U4/U6 snRNPs. 

---