Protein Functional Effector (pfe) Noncoding RNAS are Identical to Fragments from Various Noncoding RNAs

Protein functional effector (pfe)RNAs were introduced in 2015 as PIWI-interacting-like small noncoding (nc)RNAs and later categorized as a novel group. Here, we document that human 3’-end 2’-O-methylated, protein-binding pfeRNAs match fragments of Gen-Bank-database-annotated human ncRNAs. PDLpfeRNAa, matching the 3’-half fragment of a mitochondrial transfer (t)RNA, and PDLpfeRNAb, a 28S ribosomal (r)RNA fragment, bind tumor programmed death ligand (PD-L)1, respectively enhancing or inhibiting its interaction with lymphocyte PD-1, favoring or inhibiting tumor immune escape. In an 8-pfeRNA-set, validated as a pulmonary nodule presence and nature classifier, seven pfeRNAs match one or more transfer, micro, Y, PIWI, long (lnc)RNAs, and a PDLpfeRNAa fragment, with partially overlapping chromosomal locations. In a 2-pfeRNA-set distinguishing among controls, pulmonary tuberculosis, and lung cancer patients, a p60-DMAD-binding-pfeRNA affecting apoptosis complements small nucleolar RNA SNORD45C, matching smaller 18S rRNA and lncRNA segments. These sequence-identical, diversely-sourced, not-of-degradation-or-precursor-maturation-origin, multifunctional ncRNA fragments enrich the regulatory transcriptome and targetome. Differential ncRNA fragment modification may contribute to multifunctionality. For tRNA fragments, stabilizing 3’-end-2’-O-methylation, 3’-aminoacylation, and glycosylation may respectively regulate protein function, translation, and extracellular effects. One ncRNA gene can encode multiple fragments, multiple ncRNA genes can encode the same fragment, and ncRNA fragments can synergize or antagonize each other, further fostering medical applications.