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RNA Binding ProteinsComments

RNA Binding Proteins

rna binding protein rna binding domain and protein binding domain

The pre-mRNA binds many proteins during transcription. Although collectively called hnRNP proteins, they in fact belong to many different structural and functional families. Like transcription factors, RNA binding proteins can be modular and contain and RNA-binding domain and a protein-protein interacting domain.

RNA-Binding Domain

RNA-binding domains often recognize short sequences (like a base triplet) and thus have less sequence specificity than DNA-binding domains. To increase specificity, many proteins have multiple RNA-binding domains; ssRNA is flexible enough that different domains can bind the same strand. Common RNA-binding domains are shown below, in order of decreasing frequency.

DomainOverview
RRM/RNPThe RNA Recognition Motif (RRM, aka RNP domain) has an αβ structure whose β domain binds the single-stranded pre-mRNA via many backbone and base-specific interactions.
K HomologyK Homology Domains (KH Domains) are also αβ structures, although the binding surface is along the edge between α and β. Multiple KH Domains are often found in one protein.

Shuttling Between Nucleus and Cytoplasm

Some hnRNP proteins that appear to be exclusively nuclear by fluorescently staining fixed cells with antibodies (immunofluorescence) actually shuttle rapidly between the nucleus and cytoplasm, spending most of their time in the nucleus. This was observed by fusing labeled cells to unlabeled cells, and blocking protein synthesis (cyclohexamide treatment) since otherwise new proteins could get shuttled into the cytoplasm. It was seen that the unlabeled nucleus exhibits fluorescence: thus, it is apparent that the hnRNPs have shuttled out and made their way over.