Emerging role of dynamic RNA modifications during animal development.

The central dogma of molecular biology statically says that the information flows from DNA to messenger RNA to protein. But the recent advances in mass spectrometry and high throughput technology have helped the scientists to view RNA as little more than a courier of genetic information encoded in the DNA. The dynamics of RNA modifications in coding and non-coding RNAs are just emerging as a carrier of non-genetic information, uncovering a new layer of complexity in the regulation of gene expression and protein translation. In this review, we summarize about the current knowledge of N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C) and pseudouridine (Ψ) modifications in RNA, and described how these RNA modifications are implicated in early animal development and in several human diseases.

Transcription of Leishmania major U2 small nuclear RNA gene is directed by extragenic sequences located within a tRNA-like and a tRNA-Ala gene.

BACKGROUND: Leishmania and other trypanosomatid parasites possess atypical mechanisms of gene expression, including the maturation of mRNAs by trans-splicing and the involvement of RNA Polymerase III in transcription of all snRNA molecules. Since snRNAs are essential for trans-splicing, we are interested in the study of the sequences that direct their expression. Here we report the characterization of L. major U2 snRNA promoter region. RESULTS: All species of Leishmania possess a single U2 snRNA gene that contains a divergently-oriented tRNA-Ala gene in the upstream region. Between these two genes we found a tRNA-like sequence that possesses conserved boxes A and B. Primer extension and RT-qPCR analyses with RNA from transiently-transfected cells showed that transcription of L. major U2 snRNA is almost abolished when boxes A and B from the tRNA-like are deleted or mutated. The levels of the U2 snRNA were also highly affected when base substitutions were introduced into box B from the tRNA-Ala gene and the first nucleotides of the U2 snRNA gene itself. We also demonstrate that the tRNA-like is transcribed, generating a main transcript of around 109 bases. As pseudouridines in snRNAs are required for splicing in other organisms, we searched for this modified nucleotide in the L. major U2 snRNA. Our results show the presence of six pseudouridines in the U2 snRNA, including one in the Sm site that has not been reported in other organisms. CONCLUSIONS: Four different regions control the transcription of the U2 snRNA gene in L. major: boxes A and B from the neighbor tRNA-like, box B from the upstream tRNA-Ala gene and the first nucleotides of the U2 snRNA. Thus, the promoter region of L. major U2 snRNA is different from any other promoter reported for snRNAs. Pseudouridines could play important roles in L. major U2 snRNA, since they were found in functionally important regions, including the branch point recognition region and the Sm binding site.

[Combination of cancer markers in the detection and prognosis of digestive system tumors]. / Combinação de marcadores de câncer na detecção e prognóstico de tumores do aparelho digestivo.

The role of carcinoembryonic antigen (CEA), gamma glutamyl transpeptidase (gamma GT), phosphohexose isomerase (PHI), pseudouridine (PSD) and acute phase reactant proteins (C-reactive protein (C-RP], alpha 1-acid glycoprotein (alpha 1-AGP) and alpha 1-antichymotrypsin (alpha 1-ACT) in distinguishing benign from malignant conditions of the digestive tract and their value in assessing the prognosis of gastrointestinal neoplasms was evaluated. For each marker it has been possible to produce a simple scoring index derived from the values found in the control population. This work suggests that pre-operative levels of certain cancer markers may be useful in tumor detection and may also give prognostic information additional to pathological staging.