Splicing hnRNA

What is mechanistically similar between group II intron self-splicing and spliceosome-mediated hnRNA splicing ... 

Lariat The closed, circular RNA structure formed as an intermediate in RNA splicing of group II selfspliced introns and spliceosome-mediated hnRNA splicing. 

Spliceosome A large ribonucleoprotein complex that mediates hnRNA splicing. 

The processing of hnRNA molecules is a site for regulation of gene expression. Alternative patterns of RNA splicing result from tissue-specific adaptive and developmental control mechanisms. As mentioned... 

Introns are removed from hnRNA by splicing, accomplished by spliceosomes (also known as an snRNP, or snurp), which are complexes of snRNA and protein. The hnRNA molecule is cut at splice sites at the 5 (donor) and 3 (acceptor) ends of the intron. The intron is excised in the form of a lariat structuie and degraded. Neighboring exons are joined together to assemble the coding region of the mature mRNA. 

Posttranscrip-tional processing of hnRNA (pre-mRNA) None In nucleus 5 cap (7-MeG) 3 tail (poly-A sequence) Removal of introns from hnRNA Alternative splicing yields variants of protein product... 

Mutations in splice sites affect the accuracy of intron removal from hnRNA during posttran-scriptionai processing. As illustrated in Figure 1-4-4, if a splice site is lost through mutation, spliceosomes may ... 

Before the hnRNA produced by RNA polymerase II (see p. 242) can leave the nucleus in order to serve as a template for protein synthesis in the cytoplasm, it has to undergo several modifications first. Even during transcription, the two ends of the transcript have additional nucleotides added (A). The sections that correspond to the intervening gene sequences in the DNA (introns) are then cut out (splicing see B). Other transcripts—e.g., the 45 S precursor of rRNA formed by polymerase I (see p. 242)—are broken down into smaller fragments by nucleases before export into the cytoplasm. 

Immediately after transcription, the hnRNA introns are removed and the exons are linked to form a continuous coding sequence. This process, known as splicing, is supported by complicated RNA-protein complexes in the nucleus, the so-called spliceosomes. The components of these macromolecular machines... 

The domain structure in fibronectins is made up of a few types of peptide module that are repeated numerous times. Each of the more than 50 modules is coded for by one exon in the fibronectin gene. Alternative splicing (see p. 246) of the hnRNA transcript of the fibronectin gene leads to fibronectins with different compositions. The module that causes adhesion to cells contains the characteristic amino acid sequence -Arg-Gly-Asp-Ser-. It is these residues that enable fibronectin to bind to cell-surface receptors, known as integrins. 

Figure 11-4. Splicing of a eukaryotic RNA transcript. A hypothetical hnRNA with two exons (EI and E2) and a single, large intron (I) is shown. Splicing can be divided into two main reactions initial attack of ribose near an A residue within the intron on the splice donor followed by attack of the newly available 3 end of exon I (EI) on the 5 end of exon 2 (E2) with coincident release of the intron. Special sequences surround the splice donor and acceptor sites. All steps occur within the spliceosome complex.

The spliceosome. The hnRNA of nuclei, which includes all of the pre-mRNA, is associated with proteins, which sometimes form very large 200S particles.604 After limited cleavage with nucleases they tend to sediment in the 30S-40S range and to contain a variety of proteins.605 606 Some of the proteins may have been involved in control of transcription.606 Others participate in splicing. The smaller snRNP particles then appear to come into the nucleus and displace much, but not all, of the protein present in the pre-mRNA ribonucleoprotein particles.605... 

A primary transcript corresponding to the full length of the gene is first made. This is then chemically modified, and introns (two in the case of /3-globin) are removed by splicing. The mixture of primary transcripts present in the nucleus is known as heterogeneous nuclear RNA (hnRNA). 

Mature mRNA is formed by extensively modifying the primary transcript also called heterogeneous nuclear RNA (hnRNA). The hnRNA must undergo three major modifications before maturing into mRNA capping, polyadenylation and splicing. 

Splicing is the removal of noncoding sequences, derived from the DNA template, from the hnRNA to form a functional mRNA. The noncoding sequences are called introns while the coding sequences are known as exons. All introns have the sequence GU at their 5 ends and AG at their 3 ends. The guanyl residue at the 5 end of the intron is linked by a 2 to 5 phosphodiester linkage to an adenylate residue within the intron. The result is a lariat (loop) structure and the release of the 3 end of the first exon. The 3 end of the intron is spliced by an enzyme known as a spliceosome, which releases the loop and frees the 5 end of the second exon. The exons are then joined together. 

Some hnRNAs contain 50 or more exons that must be spliced correctly to produce functional mRNA. Other hnRNAs have no introns. 

A. Transcription is catalyzed by RNA polymerase II, which binds to promoter regions, including a TATA box. The DNA template strand is not covalently bound to histones. The primary transcript (hnRNA) is capped at the 5 end and polyadenylated at the 3 end introns are removed by splicing to form mRNA. 

Before RNA splicing was discovered, the nucleus was observed to contain a significant amount of seemingly untranslated RNA. The collection of RNA molecules of widely varied sizes was given the name heterogeneous nuclear RNA (hnRNA), a term that is still sometimes used for nuclear RNA. 

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