Análisis de la distribución de potenciales cuádruplex de Guanina (PQS) en el genoma de tripanosomátidos y su posible relación con el control de la expresión génica.
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2017
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Los tripanosomátidos son una familia de eucariotas unicelulares con especies causantes de
importantes enfermedades en el ser humano. Los genes de estos organismos suelen organizarse en
lo que se conoce como unidades de transcripción policistrónica (PTUs), consistente en un grupo de
genes (y secuencias intergénicas) adyacentes en la misma hebra, que se transcriben en forma
conjunta dando lugar a una única molécula de ARN (ARN policistrónico). Los ARNm maduros son
producidos a partir de los ARN policistrónicos mediante un proceso de maduración que incluye el
fenómeno de trans-splicing y poliadenilación. Actualmente se conocen pocos detalles sobre los
mecanismos de regulación de la expresión génica tanto a nivel transcripcional (inicio y terminación
de la síntesis de los ARN policistrónicos) como post-transcripcional (maduración, estabilidad y
traducción de los ARNm).
Los cuádruples de guanina son estructuras secundarias del ADN o ARN formadas en
regiones ricas en guaninas. Se ha descrito la importancia de estas estructuras en la regulación de la
expresión génica en diversos organismos.
En el presente trabajo se realizó un análisis bioinformático de la frecuencia y distribución de
cuádruples putativos de guanina (PQSs) en los genomas de distintas especies de Leishmania y
Trypanosoma, a fin de evaluar su posible impacto en la regulación de la expresión génica a nivel
transcripcional y post-transcripcional.
En Trypanosoma se observó una densidad baja de PQSs a nivel genómico con un patrón
poco claro entre las distintas especies. Por otro lado, en Leishmania se observó una mayor densidad
de PQSs a nivel genómico, con una distribución bien definida y similar entre las tres especies
analizadas. En este último género, la densidad de PQSs aumenta en la hebra molde de la región
adyacente al extremo terminal de las PTUs, por lo cual es posible que los cuádruples de guanina
puedan estar vinculados a la terminación de la transcripción. Al analizar la distribución de PQSs
dentro de las PTUs de ambos géneros, se observó una diferencia muy marcada en la densidad de
PQSs entre las secuencias génicas e intergénicas (con una muy baja densidad de PQSs en las
primeras en relación a las segundas). Esto podría ser indicio de algún rol de los cuádruples de
guanina en las etapas maduración, estabilidad y/o traducción del ARNm.
Trypanosomatids are a family of unicellular eukaryotes including species that cause important diseases in humans. Genes of these organisms are usually organized in polycistronic transcription units (PTUs). PTUs consist on a group of genes (and intergenic sequences) that are located in tandem in the same strand. They are transcribed together to form a single molecule of RNA (polycistronic RNA). Mature mRNAs are produced from polycistronic RNAs through a maturation process that includes the phenomenon of trans-splicing and polyadenylation. Currently, few details are known about the mechanisms of regulation of gene expression both at the transcriptional level (initiation and termination of polycistronic RNA synthesis) and posttranscriptional level (maturation, stability and translation of mRNAs). Guanine quadruplexes are secondary structures of DNA or RNA which are formed in regions rich in guanines. The importance of these structures in the regulation of gene expression in various organisms has been described. In order to evaluate the possible impact of guanine quadruplexes on the regulation of gene expression at transcriptional and post-transcriptional level in Trypanosomatids, we performed a bioinformatic analysis of the frequency and distribution of putative guanine quadruplexes (PQSs) in the genomes of different species of Leishmania and Trypanosoma. We observed a low density of PQSs in Trypanosoma genome, with an unclear pattern among the different species. On the other hand, we identified a higher density of PQSs in Leishmania genome with a well defined and similar distribution among the three species analyzed. In Leishmania genus, the density of PQSs increases in the region adjacent to the terminal end of the PTUs in the template strand. For that reason, we propose that guanine quadruplexes may be linked to the termination of transcription. When we analyze the distribution of PQSs within the PTUs of both genera, we observed a very marked difference in the density of PQSs between the gene and intergenic sequences (with a very low density of PQSs in the former in relation to the latter). This may indicate a role of guanine quadruplexes in maturation, stability and / or translation of the mRNA.
Trypanosomatids are a family of unicellular eukaryotes including species that cause important diseases in humans. Genes of these organisms are usually organized in polycistronic transcription units (PTUs). PTUs consist on a group of genes (and intergenic sequences) that are located in tandem in the same strand. They are transcribed together to form a single molecule of RNA (polycistronic RNA). Mature mRNAs are produced from polycistronic RNAs through a maturation process that includes the phenomenon of trans-splicing and polyadenylation. Currently, few details are known about the mechanisms of regulation of gene expression both at the transcriptional level (initiation and termination of polycistronic RNA synthesis) and posttranscriptional level (maturation, stability and translation of mRNAs). Guanine quadruplexes are secondary structures of DNA or RNA which are formed in regions rich in guanines. The importance of these structures in the regulation of gene expression in various organisms has been described. In order to evaluate the possible impact of guanine quadruplexes on the regulation of gene expression at transcriptional and post-transcriptional level in Trypanosomatids, we performed a bioinformatic analysis of the frequency and distribution of putative guanine quadruplexes (PQSs) in the genomes of different species of Leishmania and Trypanosoma. We observed a low density of PQSs in Trypanosoma genome, with an unclear pattern among the different species. On the other hand, we identified a higher density of PQSs in Leishmania genome with a well defined and similar distribution among the three species analyzed. In Leishmania genus, the density of PQSs increases in the region adjacent to the terminal end of the PTUs in the template strand. For that reason, we propose that guanine quadruplexes may be linked to the termination of transcription. When we analyze the distribution of PQSs within the PTUs of both genera, we observed a very marked difference in the density of PQSs between the gene and intergenic sequences (with a very low density of PQSs in the former in relation to the latter). This may indicate a role of guanine quadruplexes in maturation, stability and / or translation of the mRNA.
Palabras clave
Guanina, Expresión génica, Trypanosoma, Bioinformática