Alternative splicing (AS) is a major means of post-transcriptional control of gene
expression, and provides a dynamic versatility of protein isoforms. Cancer-related
AS disorders have diagnostic, prognostic and therapeutic values. Changes in the expression
and AS of human stearoyl-CoA desaturase-5 (SCD5) are promising specific tumor markers,
although the transcript variants (TVs) of the gene have not yet been confirmed. Our
in silico, in vitro and in vivo study focuses on the distribution of SCD5 TVs (A and
B) in human tissues, the functionality of the relevant splice sites, and their modulation
by certain single-nucleotide variations (SNVs). An order of magnitude higher SCD5A
expression was found compared with SCD5B. This unequal splicing is attributed to a
weaker recognition of the SCD5B-specific splicing acceptor site, based on predictions
confirmed by an optimized minigene assay. The pronounced dominance of SCD5A was largely
modified (rs1430176385_A, rs1011850309_A) or even inverted (rs1011850309_C) by natural
SNVs at the TV-specific splice sites. Our results provide long missing data on the
proportion of SCD5 TVs in human tissues and reveal mutation-driven changes in SCD5
AS, potentially affecting tumor-associated reprogramming of lipid metabolism, thus
having prognostic significance, which may be utilized for novel and personalized therapeutic
approaches.
