Welcome to another HPA image of the week! This week's image was brought to us by citizen scientists in Project Discovery, and specifically by Selphentine who pointed out several nice examples of proteins localized to "nuclear speckles". In Project Discovery, citizen scientists are refining our annotations for proteins within the nucleus by labeling these nuclear speckles, previously not annotated in the atlas.

The protein stained in Fig 1. is an image of DEAD (Asp-Glu-Ala-Asp) box polypeptide 39B (DDX39B) seen in the nuclear speckles. This sample shows MCF-7 cells, a human adenocarcinoma cell line from breast cancer.

Commonly called "nuclear speckles", these sub-nuclear structures are actually interchromatin granule clusters. These structures have been heavily studied in biology and were first described by Ramón Cajal, the father of modern neuroscience in 1910 (Cajal R. 1910)!!!

In more recent years we have come to understand that these "speckles" are clusters of small nuclear ribonucleoprotein particles (snRNPs) and other members of the "spliceosome" (Lamond A.I. & Spector D. L. 2003). Like the previously discussed nucleoli, nuclear speckles are not membrane bound, in contrast to other organelles such as the nucleus. During cell division, as the nuclear membrane breaks down, speckles become diffuse throughout the cytoplasm, though the proteins reenter the nucleus rapidly after division and reform speckles most prominent in interphase (Spector D.L. & Lamond A.I. 2011).

Your spliceosome is responsible for modifying the RNA in your cells. When transcribed from DNA, RNA contains extra pieces that don't belong to the protein the RNA codes for. These extra pieces, called "introns" need to be cut out in order for your RNA to be properly translated into a functional proteins. Once the introns are removed, the RNA is shipped from the speckles to cytoplasm and endoplasmic reticulum for translation into proteins. This process of going from DNA to RNA to proteins is so important that it is referred to as the "central dogma" of biology.

DDX39B is a member of the DEAD box protein family, a group of proteins involved in pre-mRNA splicing through RNP remodeling and the export of mRNA from the nucleus to the cytoplasm (also supported by the "additional" cytoplasmic location in DDX39B) (Linder P. 2008). Due to these interactions, DEAD box proteins are known to associate to the nuclear speckles (Saitoh N. et al. 2004).

It is not surprising that DEAD box proteins are involved in many diseases due to their role in the splicing and sorting of mRNA. In fact, some studies have shown specific DEAD box proteins are required for the transport of mRNA from the nucleus (Schmitt C.). Interestingly, a direct interaction between hepatitis C virus and the DEAD box protein DDX3 has also been observed leading researchers to speculate that the virus may use this to modulate the expression of host cell genes (Owsianka A. M. and Patel A. H. 1999).

Thanks to the citizen scientists participating in Project Discovery and particularly to Selphentine for helping us further characterize proteins with this subcellular location and for their contribution to science!

Devin Sullivan