Disease relevance of Protein Splicing

• The M. leprae protein intron provides an example of conditional protein splicing, splicing occurring in M. leprae itself but not when expressed in Escherichia coli, unlike most previously described protein introns [1].
• The A subunit of DNA gyrase in Mycobacterium leprae, unlike its counterpart in Mycobacterium tuberculosis, is produced by protein splicing as its gene, gyrA, harbors a 1260-bp in-frame insertion encoding an intein, a putative homing endonuclease [2].
• Taking advantage of recently developed in vitro systems in which protein splicing occurs in trans to assay for protein-splicing inhibitors, we discovered that low concentrations of Zn(2+) inhibited splicing mediated both by the RecA intein from Mycobacterium tuberculosis and by the naturally split DnaE intein from Synechocystis sp. PCC6803 [3].
• A method is described to express and purify human DNA (cytosine-5) methyltransferase (human DNMT1) using a protein splicing (intein) fusion partner in a baculovirus expression vector [4].
• We report extensive amino acid sequence homology between HIV-1 gp120/41, and > 33% of a U1 RNA-associated splicing protein, 70K [5].

High impact information on Protein Splicing

• Inactivation of the SR protein splicing factor ASF/SF2 results in genomic instability [6].
• Crystal structure of PI-SceI, a homing endonuclease with protein splicing activity [7].
• This report presents direct evidence for protein splicing by demonstrating in vitro splicing of purified precursor that accumulated when the protein splicing element from Pyrococcus DNA polymerase was cloned into a foreign gene [8].
• Sequence of introns and flanking exons in wild-type and box3 mutants of cytochrome b reveals an interlaced splicing protein coded by an intron [9].
• An unusual protein splicing reaction joins the N-terminal segment (A) and the C-terminal segment (C) of the 119K primary translation product (ABC) of the yeast VMA1 gene to yield a 69K vacuolar H(+)-ATPase subunit (AC) and an internal 50K polypeptide (B) [10].

Chemical compound and disease context of Protein Splicing

• Reactivity of the cysteine residues in the protein splicing active center of the Mycobacterium tuberculosis RecA intein [11].

Biological context of Protein Splicing

• The screen identified three dominant suppressor genes, one of which, CUS1-54, encodes an essential splicing protein required for U2 snRNP addition to the spliceosome [12].
• ASF/SF2 is an SR protein splicing factor that participates in constitutive and alternative pre-mRNA splicing and is essential for cell viability [13].
• Regulation of alternative splicing of CD45 by antagonistic effects of SR protein splicing factors [14].
• Crystal structure of a mini-intein reveals a conserved catalytic module involved in side chain cyclization of asparagine during protein splicing [15].
• Identification of three core regions essential for protein splicing of the yeast Vma1 protozyme. A random mutagenesis study of the entire Vma1-derived endonuclease sequence [16].

Anatomical context of Protein Splicing

• Antagonistic effects of retinoic acid and thyroid hormone on the expression of the tissue-specific splicing protein SmN in a clonal cell line derived from rat heart [17].
• Here we show that C2 cells recognize human leukocyte antigen-A3 MHC class I molecules presenting a nine-residue FGF-5 peptide generated by protein splicing [18].

Associations of Protein Splicing with chemical compounds

• C/EBPbeta -/- livers showed reduced expression of immediate-early growth-control genes including the Egr-1 transcription factor, mitogen-activated protein kinase protein tyrosine phosphatase (MKP-1), and HRS, a delayed-early gene that encodes an mRNA splicing protein [19].
• A protein splicing model is presented in which asparagine rearrangement initiates the self-excision of the spacer protein from the Tfp1 precursor [20].
• Protein splicing: an analysis of the branched intermediate and its resolution by succinimide formation [21].
• These fragments were reconstituted into a functional protein splicing element by renaturation from 6 M urea [22].
• The InRNP particles contain all uridine-rich small nuclear ribonucleoprotein complexes required for pre-mRNA splicing, as well as protein splicing factors [23].

Gene context of Protein Splicing

• Protein splicing converts the yeast TFP1 gene product to the 69-kD subunit of the vacuolar H(+)-adenosine triphosphatase [24].
• Furthermore, the 60-kilodalton subunit of SF3a is related to the yeast splicing protein PRP9 [25].
• Nova encodes a novel, highly conserved protein, homologous to the RNA-binding protein hnRNP K, the yeast splicing protein MER1, and a motif in several retroviral proteases [26].
• The mammalian analogue of the yeast PRP8 splicing protein is present in the U4/5/6 small nuclear ribonucleoprotein particle and the spliceosome [27].
• Our findings demonstrate that U1C, a well characterized splicing protein, can also function in transcriptional regulation [28].

Analytical, diagnostic and therapeutic context of Protein Splicing

• Genetic enhancement of RNA-processing defects by a dominant mutation in B52, the Drosophila gene for an SR protein splicing factor [29].
• Using Western blot analysis with antisera raised against peptides derived from the non-homology region (NHR) and the N-terminal half of the PRS1 gene product it has been shown that the NHR is not removed by protein splicing [30].

References