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Translational Regulation

Translational Regulation

Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...

Regulation of Expression Occurs at Multiple Steps

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...

Regulation of Expression Occurs at Multiple Steps

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...

Regulation of Expression at Multiple Steps

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...

Leaky Scanning

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...

Initiation of Translation

Initiation of Translation

Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...

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Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs

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Control traslacional a través de marcos de lectura abiertos regulados por proteínas aguas arriba.

Jan Medenbach¹, Markus Seiler, Matthias W Hentze

¹European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.

|June 14, 2011

Resumen

La proteína letal de sexo (SXL) regula la traducción a través de marcos de lectura abiertos aguas arriba (uORF) en el ARNm. La unión de SXL cerca de los uORF inhibe la síntesis de proteínas mediante el control de la iniciación de la traducción.

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Área de la Ciencia:

Biología Molecular Biología Molecular
Genética La genética.
Biología del desarrollo Biología del desarrollo.

Sus antecedentes:

La compensación de la dosis en Drosophila es crucial para el desarrollo sexual.
La proteína Sex lethal (SXL) juega un papel clave en este proceso.
Los mecanismos de control traslacional son vitales para la regulación de la expresión génica.

Objetivo del estudio:

Investigar el mecanismo por el cual SXL regula la traducción del ARNm msl-2.
Identificar los elementos regulatorios comunes involucrados en el control de la traducción.
Explorar la aplicabilidad más amplia de este mecanismo de regulación.

Principales métodos:

Análisis de secuencias de ARNm y regiones 5' no traducidas (UTR).
Estudiar la interacción entre SXL y las proteínas de unión al ARN.
Investigando el escaneo de ribosomas y la iniciación de la traducción en marcos de lectura abiertos aguas arriba (uORF).
Validación experimental en sistemas heterólogos.

Principales resultados:

La unión SXL aguas abajo de un uORF corto inhibe fuertemente la traducción del marco de lectura principal.
Esta inhibición se logra aumentando la iniciación del ribosoma en el uORF y obstaculizando la traducción aguas abajo.
El efecto regulador de SXL se dirige específicamente a la iniciación de la traducción, no a la prolongación o terminación.
El módulo regulador identificado funciona en un contexto biológico diferente y está presente en otros ARNm de Drosophila.

Conclusiones:

Los uORF regulados por proteínas representan un mecanismo sistemático para controlar la síntesis de proteínas.
Este modo de control traslacional, que involucra a SXL y uORF, es un hallazgo significativo en la regulación génica.
El módulo regulador descubierto tiene implicaciones para la comprensión de la expresión génica en diferentes sistemas.