User:Tianj/Influenza virus multibranch loop family

The influenza A virus multi-branch loop is a family of RNA structures formed 79 nucleotides downstream from the 5´ splice site of influenza A virus segment 7 mRNA.



Influenza A virus segment 7
Influenza A virus is a significant public health threat. Every year, 15-20% of the world's population is infected every year, and 250-500 thousand people are killed by the virus. The virus also has a potential to cause pandemics. For example, the 1918 “Spanish Flu” killed 50 to 100 million people worldwide. The unspliced segment 7 mRNA of influenza A virus encodes the M1 protein, which is the matrix protein that underlines the virion envelop. Segment 7 mRNA can be alternatively spliced, and produce up to three proteins (including M1). The main spliced product is the M2 ion channel protein. In some viral strains, it can also produce M42 protein, which functions similarly to M2.

The multi-branch loop family
The multi-branch loop family was first predicted by a bioinformatics survey based on thermodynamics, sequence comparison, and suppression of synonymous codon usage. The secondary structure was experimentally verified by native gel electrophoresis, in vitro enzymatic/chemical probing and NMR. This structure is highly-conserved (93.6% average pairwise sequence identity) throughout influenza A strains. Most nucleotides in P2 and P3 are more than 97% conserved. In P1 and P1a, about 1/3 mutations retain canonical pairing. When mutations lead to noncanonical pairs, about 1/3 are CA pairs, which are able to maintain the A-form RNA helix. A putative intronic splicing enhancer GGGGAUU (nt 171 to 177) and a potential M4 mRNA 5´ splice site GAG/GUUCUC (nt 118 to 126) are buried in the helical region, making them less accessible to the splicing machinery. P1a and P3 appear to be flexible, which may be important for organizing tertiary structure and putting splicing regulatory motifs into different structural context. This family may play an important role in the alternative splicing of segment 7.