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12 recordsLinked to original sources
PubMed2025

A novel regulation on the developmental checkpoint protein Sda that controls sporulation and biofilm formation in Bacillus subtilis.

UNLABELLED: Biofilm formation by Bacillus subtilis is triggered by an unusually simple environmental sensing mechanism. Certain serine codons, the four TCN codons (N for A, T, C, or G), in the gene for the biofilm repressor SinR caused lowered SinR translation and subsequent biofilm induction during transition from exponential to stationary growth. Global ribosome profiling showed that ribosomes pause when translating the four UCN (U for T on the mRNA) serine codons on mRNA, but not the two AGC/AGU serine codons. We proposed a serine codon hierarchy (AGC/AGT vs TCN) in that genes enriched in the TCN serine codons may experience reduced translation efficiency when serine is limited. In this study, we designed an algorithm to score all protein-coding genes in B. subtilis NCIB3610 based on the serine codon hierarchy. We generated a short list of 50 genes that could be subject to regulation by this novel mechanism. We further investigated one such gene from the list, sda, which encodes a developmental checkpoint protein regulating both sporulation and biofilm formation. We showed that synonymously switching the TCN serine codons to AGC in sda led to delayed biofilm formation and sporulation. This engineered strain also outgrew strains with other synonymously substituted sda alleles (TCN) in competition assays for biofilm formation and sporulation. Finally, we showed that the AGC serine codon substitutions in sda elevated the Sda protein levels. This serine codon hierarchy-based novel signaling mechanism could be exploited by bacteria in adapting to stationary phase and regulating important biological processes. IMPORTANCE: Genome-wide ribosome profiling in Bacillus subtilis shows that under serine limitation, ribosomes pause on the four TCN (N for A, C, G, and T), but not AGC/AGT serine codons, during translation at a global scale. This serine codon hierarchy (AGC/T vs TCN) differentially influences the translation efficiency of genes enriched in certain serine codons. In this study, we designed an algorithm to score all 4,000+ genes in the B. subtilis genome and generated a list of 50 genes that could be subject to this novel serine codon hierarchy-mediated regulation. We further investigated one such gene, sda, encoding a developmental checkpoint protein. We show that sda and cell developments controlled by Sda are also regulated by this novel mechanism.

Bacillus subtilis↗
PubMed1978

Spontaneous somatic mutations. Structural studies on mutant immunoglobulins.

The precise alterations in the protein amino acid sequences of the immunoglobulin heavy chains of spontaneously arisen MOPC 21 mutant clones IF2 and IF1 have been determined. All the cyanogen bromide fra-ments of both heavy chains have been isolated and compared to the wild type CNBr fragments. For IF2, there is an internal deletion, from the wild type sequence, of 96 amino acids, from residues 121 to 215 inclusive. Moreover, in IF2, there are no disulfide bonds formed between heavy and light chains, presumably because of the deletion of the CH1 pseudosubunit. There are no other alterations in its covalent structure. For IF1, there is a deletion of the COOH-terminal 83 amino acids (residues 358 to 440, inclusive). Although IF1 heavy chain behaves on dodecyl sulfate-polyacryl-amide gels as if it were only 10 to 15 residues shorter than wild type, no other amino acid sequence differences from wild type are found. IF1 arose most likely by a nonsense mutation of a serine codon. For IF2, whose deletion is like that seen in some human heavy chain disease proteins, the most likely explanation is an error of recombination. The structure of IF2 suggests that the heavy chain variable region ends at a position homologous to residue 120 of the MOPC 21 heavy chain.

Amino Acids↗
PubMed1977

Nonsense suppressors of yeast cause osmotic-sensitive growth.

Many nonsense suppressors of Saccharomyces cerevisiae cause growth inhibition on hypertonic media. Eight tyrosine-inserting UAA (ochre) suppressors, eight tyrosine-inserting UAG (amber) suppressors, a leucine-inserting UAG suppressor, and a serine-inserting recessive lethal UAG suppressor cause osmotic sensitivity, whereas a serine-inserting UAA suppressor does not cause sensitivity. Although the mechanism is not understood, the growth inhibition of specific suppressors on hypertonic media is correlated with their efficiencies of suppression. This heretofore unknown property of nonsense suppressors is useful for mitotic mapping, selecting tRNA mutants, selecting antisuppressors, and scoring nonsense suppressors.

Codon↗
PubMed1975

Amino acid composition of proteins: Selection against the genetic code.

Distribution of amino acids in 68 representative proteins is compared with their distribution among 61 codons of the genetic code. Average amounts of lysine, aspartic acid, glutamic acid, and alanine are above the levels anticipated from the genetic code, and arginine, serine, leucine, cysteine, proline, and histidine are below such levels. Arginine plus lysine account for 11.0 percent of codons and aspartic acid plus glutamic acid account for 11.3 percent; thus the average charge is roughly neutral.

Amino Acid Sequence↗
PubMed1976

Isoaccepting species of serine tRNA coded by bacteriophage T5sto.

By aminoacyl-tRNA-DNA hybridization and chromatographic analysis, evidence was provided that the bacteriophage T5stO codes for two tRNAser species. Trinucleotide- or polynucleotide-stimulated binding experiments assigned the codons UCC or UCU to these two tRNAser species. They also suggested that the synthesis of these two tRNAser species does not modify the reading capacity for codons less used in Escherichia coli F and corresponds to a different situation compared with the T4-coded tRNA's.

Coliphages↗
PubMed1977

Structure of human hemoglobin messenger RNA and its relation to hemoglobinopathies.

1. One-fifth to 1/4 of globin mRNA is untranslated sequence other than polyadenylic acid. 2. The untranslated sequences of mRNA vary markedly in their sequence and in their length. 3. Globin mRNAs demonstrate a marked bias in codon selection. 4. Viral mRNA shows a quite different pattern of codon selection; therefore, the selection of codons is not uniform for all mRNAs functioning in animal cells. 5. Elongated hemoglobin chains can be accounted for by frame-shift mutations, or point mutations within the normal termination codon. The additional amino acids are then coded for by sequences that are normally untranslated. 6. Certain hemoglobin deletion mutants occur at sites where there are partially reiterated sequences within the heomoglobin messenger RNA.

Base Sequence↗
PubMed1979

In vitro suppression of UAG and UGA mutants in the thymidine kinase gene of herpes simplex virus.

We have studied the in vitro translation, in nuclease-treated reticulocyte lysates, of mRNA from cells infected with several thymidine kinase-deficient mutants of herpes simplex virus type I. The addition of suppressor tRNAs from yeast resulted in suppression of the mutant property in the case of two mutants. Synthesis of enzymatically active viral thymidine kinase was restored by serine-inserting amber suppressor tRNA in the case of HSV TK4- and synthesis of the intact, but inactive, thymidine kinase protein was restored by serine- and leucine-inserting UGA suppressor tRNAs in the case of HSV TK43-. Read-through of the normal termination at the end of the thymidine kinase gene was promoted by UGA suppressor tRNAs. We conclude that HSV-TK4- is an amber (UAG) mutant and that HSV-TK43- is an opal (UGA) mutant.

Cell-Free System↗
PubMed2026

An antisense antidote to oncogenic poison exons.

Splicing factors are frequently mutated in myeloid cancers, causing splicing aberrations that derail the expression of tumor suppressor genes. In SRSF2 mutated cancers, a key oncogenic splicing event is the inclusion of a "poison" exon that introduces an early stop codon in EZH2 mRNA, causing its destabilization. In this issue of Genes & Development, Islam et al. (doi:10.1101/gad.353628.126) define how mutant SRSF2 binding to the poison exon mediates its inclusion and identify an antisense oligonucleotide that represses the exon to restore EZH2 function and rescues hematopoietic defects. Thus, targeting of poison exons, many of which show protumorigenic and antitumorigenic properties, is a promising new avenue to treat cancer.

Oligonucleotides, Antisense↗
PubMed1977

Initiation of polypeptide synthesis with various NH2-blocked aminoacyl-tRNAs under the direction of alfalfa mosaic virus RNA 4.

Initiation of polypeptide synthesis in a cell-free system of Escherichia coli directed by alfalfa mosaic virus RNA 4 was studied by using either fMet-tRNA or Ac-Phe-tRNA as initiator tRNA. Initiation with fMet-tRNA yielded a product that was identical to the authentic viral coat protein except that the NH2-terminal serine was preceded by fMet instead of being acetylated. When Ac-Phe-tRNA was used as initiator, the biosynthetic product was 10-12 amino acid residues longer, the extra amino acids being located at the NH2-terminus. fMet-tRNA and Ac-Phe-tRNA did not compete for ribosomes during initiation of protein synthesis, as became evident from incorporation studies using both initiator tRNAs simultaneously. It is concluded that E. coli ribosomes recognize two sites on the 5' end of alfalfa mosaic virus RNA 4 that are separated by a region of about 30 nucleotides. The results are in complete agreement with the 5'-terminal nucleotide sequence of this RNA [Koper-Zwarthoff, E. C., Lockhard, R. E., RajBhandary, U. L., Alzner-deWeerd, B. & Bol, J. F. (1977) Proc. Natl. Acad. Sci. USA 74, 5504-5508].

Cell-Free System↗