ISOFORMS

The NRP1 has 30 isoforms according to AceView; 23 alternatively spliced mRNA variants and 7 unspliced mRNA variants. These isoforms are labeled a through u and va through vi Basic information will be given on all isoforms, but detailed information and diagrams will only be given on two isoforms- isoform a and isoform i (8).

Isoform a was chosen for several reasons, most notably because it is the longest known isoform of NRP1. This isoform has 17 exons within the transcript and a coding sequence length of 2772 base pairs. It codes for a complete protein, 923 aa in length, which is highly expressed and typically localized in the cell membrane. Also, it is important to note that isoform a is very similar to many other isoforms, essentially only differing based on different 5’ and 3’ UTR lengths (8).

Isoform i was chosen because it also translates to a complete protein and is very similar to isoform a, except that it is shorter. We thought isoform i was an interesting one because even though it is nearly identical to isoform a, it lacks the MAM domain and transmembrane domain found in isoform a. Since this isoform lacks the transmembrane domain the protein it encodes has a different sublocalization than the isoform a protein; it is a secreted or extracellular protein. We thought it would be interesting to focus on two isoforms that code for proteins with different sublocalization regions. Since this isoform is secreted it contains an N terminus signal peptide from amino acids 1 through 22 (8).

Isoform Table - Spliced Variants

This isoform table represents general information about all of the spliced variants and the data was provided through AceView (8).

Isoform Table - Unspliced Variants

This isoform table represents general information about all of the unspliced variants and the data was provided through AceView (8).

These two tables combined represent all 30 of the known gene isoforms for Neuropilin-1. The total number of exons range from 1-17 and the lengths of these exons are drastically different for different isoforms. Due to these differences in the number of exons and their sizes, the corresponding CDS length and protein products vary among all isoforms. For example, isoform a has 17 exons and codes for a protein that is 923 amino acids in length while isoform vi has 2 exons and codes for a protein that is only 28 amino acids in length. In addition to these differences, the UTRs also exist across a wide range of lengths. Another big difference observed when comparing all of the isoforms is that some of them do not have all of the domains seen in other isoforms. For example, isoform a has a transmembrane domain, two CUB domains, two F5/8 type C domains, and a MAM domain while isoform l only has a MAM domain. These different domains can correspond to different functions of the protein product, so clearly many of these isoforms have different functions from one another. Due to these differences, it means that different variants may be expressed differently because their protein products will be different from one another and serve different functions. These are just a few differences we chose to point out among the different isoforms but as you can see from the table, they also differ in many other aspects as well (8).

Isoform Diagrams

We used information from AceView to format the following diagrams (8).

Neuropilin-1 Isoform a pre-mRNA diagram

Neuropilin-1 Isoform i pre-mRNA diagram

Composite Table of pre-mRNA Isoforms a and i

This composite table was compiled from information available on AceView (8).