Usuari:BQUB13-Evayreda/SON protein

PRESENTATION

SON is the name that has been given to a large Ser/Arg (SR)-related protein, which is a splicing co-factor that contributes to an efficient splicing within cell cycle progression. (1)

It can also be called BASS1 (Bax antagonist selected in saccharomyces 1) or NRE-binding protein (Negative regulatory element-binding protein). The most common gene name of this splicing protein- which is only found in Humans (Homo sapiens)- is SON, but C21orf50, DBP5, KIAA1019 and NREBP can also be used as synonyms. (3)

STRUCTURE

The sequence length of the SON protein consists in 2426 aa and its sequence status is totally completed. Its molecular weight is 263,830 Daltons (Da) and its domain contains 8 types of repeats which are distributed in 3 regions. This protein is found in the 21st chromosome and is mostly located in Nucleus speckle. Its higher expression is seen in leukocyte and heart. (3) (6)

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  Location of the Gene that encodes the SON protein.

SPLICING PROCESS

Splicing is known as the process within the maturation of the pre-RNAm takes place. The pre-RNAm which has just been transcript has sequences called introns and exons. Introns are non-active nucleotide sequences that have to be removed in order the exons (active sequences) to get joined. This process must be very controlled. The splicing takes place in the spliceosome, a complex that brings together a pre-RNAm and a variety of the binding proteins. These proteins together with the splicing factors (which are not found in the spliceosome) are in charge of recognizing the intron’s branch point sequence. The SON protein is known to be one of these binding proteins. (5)

Although there is a lack of knowledge about its exact splicing control in the progression of the cell cycle and it has remained largely unexplored, it’s certain that this splicing-associated protein is necessary for the maintenance of the embryonic stem cells because it influences the splicing of pluripotency regulators. (1) (2)

Human embryonic stem cells are able to undergo the process of differentiation into specific and relevant cells. To maintain the pluripotency of the embryonic stem cells, transcription factors and epigenetic modifiers play an important role despite the fact that little is known about the regulation of pluripotency throughout the process of splicing. The factor SON is identified as essential for the maintenance of this pluripotency. It is confirmed that SON regulates the splicing process of transcripts (RNAm) that will encode the gens that are going to regulate the pluripotency of the embryonic human cells. (7)

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  SON protein's intervention in the splicing process.

FUNCTIONS

On the one hand, SON protein is required to maintain the genome stability in order to ensure an efficient RNA processing of affected genes. It also facilitates the interaction of SR proteins with RNA polymerase II and is required for processing of weak constitutive splice sites, having also strong implications in cancer and other human diseases. (1) (6)

On the other side, a deficiency or knockdown of SON protein causes various and severe defects in mitotic division arrangement, chromosome alignment and microtubule dynamics when spindle pole separation takes place. (1)

But as we could read in the article called “SON protein regulates GATA-2 through transcriptional control of the microRNA 23a-27-24-a clúster”, SON protein has even more functions in the organism. It has been found that these proteins may regulate the hematopoietic cells differentiation. They have a specific job in hematopoietic process, which is based on activating other proteins called GATA. As these ones are finally activated, the cell differentiation starts normally. (4)