RNA nuclear

In contrast, RNA occurs in multiple copies and various forms (Table 11.2). Cells contain up to eight times as much RNA as DNA. RNA has a number of important biological functions, and on this basis, RNA molecules are categorized into several major types messenger RNA, ribosomal RNA, and transfer RNA. Eukaryotic cells contain an additional type, small nuclear RNA (snRNA). With these basic definitions in mind, let s now briefly consider the chemical and structural nature of DNA and the various RNAs. Chapter 12 elaborates on methods to determine the primary structure of nucleic acids by sequencing methods and discusses the secondary and tertiary structures of DNA and RNA. Part rV, Information Transfer, includes a detailed treatment of the dynamic role of nucleic acids in the molecular biology of the cell. 

In all eukaryotic cells there are small nuclear RNA (snRNA) species that are not directly involved in protein synthesis but play pivotal roles in RNA processing. These relatively small molecules vary in size from 90 to about 300 nucleotides (Table 35-1). 

Small nuclear RNAs (snRNAs), a subset of these RNAs, are significantly involved in mRNA processing and gene regulation. Of the several snRNAs, Ul, U2, U4, U5, and U6 are involved in intron removal and the processing of hnRNA into mRNA (Chapter 37). The U7 snRNA may be involved in production of the correct 3 ends of histone mRNA—which lacks a poly(A) tail. The U4 and U6 snRNAs may also be required for poly(A) processing. 

All eukaryotic cells have four major classes of RNA ri-bosomal RNA (rRNA), messenger RNA (mRNA), transfer RNA (tRNA), and small nuclear RNA (snRNA). The first three are involved in protein synthesis, and snRNA is involved in mRNA splicing. As shown in Table 37-1, these various classes of RNA are different in their diversity, stability, and abundance in cells. 

Spliceosome The macromolecular complex responsible for precursor mRNA splicing. The spliceosome consists of at least five small nuclear RNAs (snRNA Ul, U2, U4, U5, and U6) and many proteins. 

Heterogeneous kinetic rate law, 25 286 Heterogeneous nuclear RNA (hnRNA), 22 454... 

A rigorous structural proof of the insecticidal exotoxin (34) from Bacillus thurin-giensis has now been published,107 confirming the a-configuration of the glucosidic bond. The total synthesis of (34) is further confirmation of the correctness of the structural assignment.108 The exotoxin inhibits RNA synthesis in insects and animals and affects the incorporation of orotic acid into nuclear RNA.109... 

TapCT The C-terminus of the mammalian nuclear RNA export factor NXFl/2 (also known as Tap) contains a sequence region with significant similarity to UBA-like domains. This region is also found in the yeast RNA export factor Mex67. A three-dimensional structure of this domain is available and confirms its similarity to the UBA domain [68]. This UBA-like domain does not appear to bind to ubiquitin but rather to the Phe-Gly repeat motif found in a number of nu-cleoporins. The interaction surface of the UBA-like TapCT domain with a Phe-Gly-containing loop was mapped by an NMR/X-Ray combination technique and shown to be different from the ubiquitin-binding mode the Phe-Gly loop binds on the backside of the UBA-like domain and is in contact with helices a2 and a3 [68]. 

Heterogeneous nuclear RNA (huRNA or pre-mRNA), which is found only in the nucleus of eukaryotic cells. It represents precursors of mRNA, formed during its post-transcriptional processing. 

Small nuclear RNA (snRNA), vrfiich is also only found in the nucleus of eukaryotes. One of its major functions is to participate in splicing (removal of introns) mRNA. 

A stretch of DNA that is transcribed as a single continuous RNA strand is called a transcription unit. A unit of transcription may contain one or more sequences encoding different polypeptide chains (translational open reading frames, ORF) or cistrons. The transcription unit is sometimes termed the primary transcript, pre-messenger RNA or heterogeneous nuclear RNA (hnRNA). The primary transcript is further processed to produce mRNA in a form that is relatively stable and readily participates in translation. In order to understand the primary need for processing of this RNA, the biochemical definition of a gene must be discussed. 

The mammalian inactive X-chromosomes in females is associated with H3 methylated at Lys-9 but does not have H3 methylated at Lys-4 [165,166]. Deletion of murine Suv39h genes does not affect H3 Lys-9 methylation at the inactive X-chromosome. Thus, different histone methyltransferases are involved in the methylation of H3 Lys-9 in constitutive and facultative heterochromatin [166]. Further, HPl is not associated with the inactive X-chromosome. Methylation of H3 Lys-9 is an early event in X inactivation in mammals [167,168]. The H3 Lys-9 methylation occurs approximately at the same time as H3 Lys-9 hypoacetylation and Lys-4 hypomethylation, and happens before transcriptional inactivation of the X-linked genes. Upstream of the Xist gene, which codes for a strictly nuclear RNA involved in X inactivation, is a constitutive hotspot of H3 methylated at Lys-9. This early event of H3 Lys-9 methylation occurs simultaneously with or immediately following the association of Xist RNA with the X-chromosome. It has been proposed that the hotspot upstream of the Xist gene serves as a nucleation site for the spreading of Xist RNA and methylated Lys-9 H3 [167]. 

Fakan, S. and Bernhard, W. (1971) Localisation of rapidly and slowly labelled nuclear RNA as visualized by high resolution autoradiography. Exp. Cell. Res. 67(1), 129-141. 

Hendzel, M.J., Kruhlak, M.J., and Bazett-Jones, D.P. (1998) Organization of highly acetylated chromatin around sites of heterogeneous nuclear RNA accumulation. Mol. Biol. Cell. 9(9), 2491-2507. 

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... 

Small nuclear RNAs (snRNAs) are involved in the splicing of mRNA precursors (see p.246). They associate with numerous proteins to form spliceosomes. ... 

In eukaryotes, mRNAs are initially transcribed as heterogeneous nuclear RNA, which still contains intervening sequences of the gene and must undergo processing to attain the final mRNA structure. 

E. Small nuclear RNA (snRNA) molecules are components of splicesomes, which... 

Figure 11-3. The prokaryotic RNA transcription bubble. RNA pol II, RNA polymerase II hnRNA, heterogeneous nuclear RNA.

The RNA product may encode transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), or small nuclear RNAs (snRNAs) that have end point functions in the cell. 

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