Nereis. Interdisciplinary Ibero-American Journal of Methods, Modelling and Simulation.


Role of the PNPase enzyme in the transport of mtRNA in lymphatic cancer: Bibliographic review



Lymphoma is the most common type of blood cancer today and, as its name suggests, it begins in the lymphatic system. The origin of this disease is related to mitochondrial defects, generated by mutations in the PNPase enzyme or polynucleotide phosphorylase, whose main functions are to import and degradation mitochondrial RNA. For this reason, the main objective of the present work was to carry out a bibliographic review of scientific publications that made the role of this enzyme relevant, in relation to mitochondria as the cause of lymphatic cancer.

The methodology used consisted of a bibliometric analysis based on the use of different databases, in which search equations formed from keywords were introduced. Then, the selection of articles related to the study topic and published in the last 20 years was carried out. Subsequently, the journals were analyzed, based on the H index, in order to observe which supported the hypothesis of the role of PNPase in lymphoma and which stated the opposite.

The results showed that a total of 441,288 scientific publications were obtained, of which 133 were selected to carry out this work. As for the journals, those with the highest H index were Nature and Cell.

It can be concluded that PNPase plays a very important role in the transport of mitochondrial RNA, and that the factor NF-Y is involved in the control of cell growth, therefore, both have a crucial role in the development of this disease. Therefore, research on both PNPase and NF-Y is essential to establish the specific genetic characteristics that define the early lesions of lymphatic cancer and the consequent determination of their treatment.


Vander AJ, James H, Sherman DS, Luciano. Human Physiology, 6th Edition. McGraw-Hill, Inc.NY. 1994.

Connect E. Anatomía del sistema linfático: componentes y funciones. 2019.

Fleisher TA, Shearer WT, Schroeder HW, Frew AJ, Weyand CM, Rich RR. Inmunología clínica.Principios y práctica. Quinta edición. Elsevier. 2019.

Pérez-Zúñiga JM, Aguilar-Andrade C, Álvarez-Vera JL, Augusto-Pacheco M, Báez-IslasPE, Bates-Martín RA, et al. (2018). Generalidades sobre linfomas. Revista de Hematología.2018;19:174-188.

Walter J. La guía sobre el linfoma. Información para pacientes y cuidadores. Leukemia & LymphomaSociety. 2014.

Albarrán B, Caballero D, Cabezudo M, Cabo E, Cidoncha B, Fernández S, et al. Guía de linfomas.ISBN: 978-84-940139-6-6. DL: M-22628-2017. Doing Soluciones Graficas S.A. 2017.

Antón Rodríguez Á y Desvaux García M. Factores pronósticos en el linfoma de Hodgkin. Revisiónde una serie clínica. 2019.

Cuezva JM, Ortega AD, Willers I, Sanchez-Cenizo L, Aldea M, SanchezArago M. The tumorsuppressor function of mitochondria: translation into the clinics. Biochim Biophys Acta.2009;1792:1145-1158.

Formentini L, Martinez-Reyes I, Cuezva JM. The mitochondrial bioenergetic capacity of carcinomas.IUBMB Life. 2010;62:554-560.

Galluzzi L, Kepp O, Heiden MGV, Kromer G. Metabolic targets for cancer therapy. Nat RevDrug Discov. 2013;12:829-46.

Valle A y Soto I. Metabolismo energético y cáncer. Vertientes Rev Esp en Ciencias de la Salud.2014;17:108- 13.

Freyre-Bernal SI, Saavedra-Torres JS, Zúñiga-Cerón LF, Salguero C. Cáncer y mitocondria: unaspecto central. 2017.

Warburg O, Posener K, Negelein E. Uber den Stoffwechsel der Tumoren. BiochemischeZeitschrift. 1924;152:319–44.

Mendiola AV y Soto Cruz I. Metabolismo energético y cáncer. Vertientes Revista Especializadaen Ciencias de la Salud. 2014;17:108-113.

Wang G, Shimada E, Koehler CM, Teitell MA. PNPASE and RNA trafficking into mitochondria.Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms. 2012;1819:998-1007.

Golzarroshan B, Lin CL, Yang WZ, Chu LY, Agrawal S, Yuan, H. S. Crystal structure of dimerichuman PNPase reveals why disease-linked mutants suffer from low RNA import and degradationactivities. Nucleic acids research. 2018;46:8630-8640.

Jeandard D, Smirnova A, Tarassov I, Barrey E, Smirnov A & Entelis N. Import of non-codingRNAs into human mitochondria: A critical review and emerging approaches. Cells. 2019;8:286.

Cameron TA, Matz LM, De Lay NR. Polynucleotide phosphorylase: Not merely an RNase buta pivotal post-transcriptional regulator. PLoS genetics. 2018;14.

Lin CL, Wang YT, Yang WZ, Hsiao YY, Yuan HS. Crystal structure of human polynucleotidephosphorylase: insights into its domain function in RNA binding and degradation. Nucleic AcidsRes. 2012;40:4146-4157.

Wang G, Chen HW, Oktay Y, Zhang J, Allen EL, Smith GM, et al. PNPASE regulates RNAimport into mitochondria. Mol. Cell. 2010;142:456-467.

Fukuhara N, Tagawa H, Kameoka Y, Kasugai Y, Karnan S, Kameoka J, et al. Characterizationof target genes at the 2p15-16 amplicon in diffuse large B-cell lymphoma. Cancer Science.2006;97:499-504.

Yu YL, Chou RH, Wu CH, Wang YN, Chang WJ, Tseng YJ, et al. Nuclear EGFR suppressesribonuclease activity of polynucleotide phosphorylase through DNAPK-mediated phosphorylationat serine 776. Journal of Biological Chemistry. 2012;287:31015-31026.

Sachini N & Papamatheakis J. NF-Y and the immune response: dissecting the complex regulationof MHC genes. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms.2017;1860:537-542.

Van der Watt PJ & Leaner VD. The nuclear exporter, Crm1, is regulated by NFY and Sp1 incancer cells and repressed by p53 in response to DNA damage. Biochim. Biophys. Acta BBAGene Regul. Mech. 2011;1809:316-326.

Imbriano C, Gnesutta N & Mantovani R. The NF-Y/p53 liaison: Well beyond repression. Biochim.Biophys. Acta BBA Rev. Cancer. 2012;1825:131-139.

Dolfini D, Andrioletti V & Mantovani R. Overexpression and alternative splicing of NF-YA inbreast cancer. Scientific reports. 2019;9:1-12.

Rius R, Van Bergen NJ, Compton AG, Riley LG, Kava MP, Balasubramaniam S, et al. ClinicalSpectrum and Functional Consequences Associated with Bi-Allelic Pathogenic PNPT1 Variants.Journal of clinical medicine. 2019;8.

Belluti S, Semeghini V, Basile V, Rigillo G, Salsi V, Genovese F, et al. An autoregulatory loopcontrols the expression of the transcription factor NF-Y. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms. 2018;1861:509-518.

Liu X, Fu R, Pan Y, Meza-Sosa KF, Zhang Z, Lieberman J. PNPT1 release from mitochondriaduring apoptosis triggers decay of poly(A) RNAs. Cell. 2018;174:187–201.e112.


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