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 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.
| Domain | Overview |
| RRM/RNP | The 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. |
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| K Homology | K 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. |
| Next Steps | Read about DNA Binding Proteins. |
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Introns have sequences that directs the splicing apparatus during RNA splicing, part of RNA processing:
| Introns begin and end with splice sites that conform to consensus sequences. |
| Introns always begin with a GU encompassed within a larger 5’ splice site consensus. |
| Introns always end with the branch point sequence, several pyrimidines and an AG. |
Below are examples of different types of DNA-binding proteins. The most common and best studied DNA-binding proteins are the Zinc finger proteins, the Helix-turn-helix proteins, and the Leucine zipper proteins.
| TATA Box Binding Prtn | The TATA box binding protein is a subunit of the eukaryotic transcription factor, TFIID. This protein is somewhat unusual in that its TBP-binding domain binds to the minor groove of DNA. |
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| Zinc finger domain | This domain is common in eukaryotic DNA-binding proteins. It was first noticed in the eukaryotic transcription factor, TFIIIA. TFIIIA contains 9 repeated modules, each of which contains two Cysteine and two Histidine residues. These four residues chelate one Zn++ ion. Each finger is bound in the major groove of B-DNA. |
| Helix-turn-helix domain | This motif was first noticed as a feature of the crystal structure of the bacteriophage l Cro protein. The structure of this small regulatory protein contained two a-helices separated by 34 Ã… – the pitch of a DNA double helix. Model building studies showed that these two a-helices would fit into two successive major grooves. As the structures of a number of other bacterial regulatory proteins (the CRP protein and the bacteriophage l cI repressor) were solved, the same structural motif – called a helix-turn-helix – was observed. It consists of two a-helices separated by a short turn (it is not a b turn). One helix binds to recognition elements within the major groove of DNA; the other helps to keep the binding helix properly positioned with respect to the rest of the molecule. This motif, common in bacterial DNA-binding proteins, also occurs in the eukaryotic homeobox proteins. |
| Leucine Zipper domains | This domain is an important feature of many eukaryotic regulatory proteins. Leucine is an hydrophobic amino acid. When it occurs at every seventh position of an a-helix, the aliphatic side-chains are all oriented on the same side of the helix and they can interact with another such helix to form a coiled coil type of structure. The GCN4 transcription activator in yeast is a dimer in which the leucine zipper region helps to position the two basic regions that bind to the DNA recognition sequence. |
| Helix-Loop-Helix binding motif | A variation of the leucine zipper, the basic DNA-binding helices are connected to the dimerization helices by a short loop. |
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